As far as I am aware, all eukaryotic membranes consist of a lipid bilayer. Smooth endoplasmic reticulum (ER) and rough ER are distinguished by the presence of ribosome on the rough ER surface, but are apparently otherwise similar. So what causes ribosomes to associate with the membrane of rough ER but not that of smooth ER. Or do ribosomes convert smooth ER to rough ER by binding to their membranes?
Peptides that are destined to be either secreted or included in the cell membrane have a signal sequence that binds a protein called Signal Recognition Particle (SRP). The SRP will in turn bind to translocons--basically peptide tunnels in the RER membrane. You need to have this interaction between the translocon and the SRP in order to have stable ribosome attachment. That's why you won't have ribosomes attaching to other membranes. After attachment the ribosome will continue translating mRNA through the translocon into the RER lumen.
Now here's where things get a bit dicey. If the resulting structure in the RER lumen is largely hydrophilic then it will stay in the RER lumen where it will later be targeted to wherever it needs to go based on other signal sequences.
However, if there are large stretches of hydrophobic residues, then those don't like to be in the aqueous environment of the ER lumen. Ergo they will incorporate into the RER membrane. Thus they become transmembrane proteins. A good rule of thumb is that if you have 10 hydrophobic residues in a row, then there's a good chance that is going to get incorporated into a membrane.
Once protein transcription is complete the ribosome will no longer be associated with the RER and will re-enter the pool of free ribsomes (ready to pick up a new mRNA).
EDIT: In response to question in comments about why translocons are found in RER and not in other membranes
You can certainly ask the question, but you're getting close to falling into that beautiful genesis of basic science research: something I call the 'why-hole'. I searched around, and I don't think we have a full understanding of membrane organization throughout the cell, though I would defer to any cell biologists who have a better understanding. We do have some idea of the mechanisms. What follows is a stitching together of hypothesis and some facts I was able to find.
It stands to reason that since the translocon is a complex of transmembrane proteins, its parts were at some point synthesized by a ribosome through a previous translocon. That would get it into the RER membrane. Now in order for a piece of membrane (or anything within the ER lumen, for that matter) to get to its final destination it has to have another signal sequence. This signal sequence will be recognized by unique signal recognition protein. This will localize the protein to a part of the RER that has several proteins that will form a vesicle (one of which being clathrin) and a protein attached to it called a v(esicle)-SNARE. Once the vesicle buds off it will go through the cell until its v-SNARE runs into a t(arget)-SNARE. This interaction will ultimately lead to fusion of the vesicle into the target membrane (e.g. lysosome, plasma membrane, etc). I double checked all of my facts here, where you can read more about it.
All of this is to say that if a transmembrane protein doesn't have a signal sequence it won't get targeted for transport through this system and should stay in the endoplasmic reticulum.
At this point it would be good to remind everyone that the ER--both rough and smooth--is a continuous structure with the RER located closer to the nucleus and the SER closer to the cell membrane. So it would be reasonable to ask why translocons stay in the RER and doesn't diffuse into the SER. That's where we get into more emerging science. From what I gather there are many proteins that are involved in the strutrue and organization of the ER. You can look into "the ability of NDPK-B to form microdomains at the membrane level" or reticulon2, but I think there's still a fair amount of work to do in this field. I encourage you to look into these resources, and if this is something that you're interested in consider doing some research. There is some evidence that membrane dysfunction is associated with neuronal disease, so any advances would be well received.
As always, keep asking questions!
Pituitary gonadotropes are immunolabeled fluorescent green for LH (see above banner) and nuclei stain blue with DAPI. However, in the above view, they are dual labeled for Cre-recombinase with dylight 594 (red) in the nuclei and cytoplasm. This makes the nuclei purple and the cytoplasm yellow.
5 nM Gold markers detect LH in the Golgi complex and in a secretory granule.
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Human ribophorins I and II: the primary structure and membrane topology of two highly conserved rough endoplasmic reticulum-specific glycoproteins.
Ribophorins I and II represent proteins that are postulated to be involved in ribosome binding. They are abundant, highly-conserved glycoproteins located exclusively in the membranes of the rough endoplasmic reticulum. As the first step in the further characterization of the structure and function of these proteins, we have isolated and sequenced full-length human cDNA clones encoding ribophorins I and II using probes derived from a human liver expression library cloned into pEX1. The authenticity of the clones was verified by overlaps in the protein sequence of N-terminal and several internal fragments of canine pancreatic ribophorins I and II. The cDNA clones hybridize to mRNA species of 2.5 kb in length, and encode polypeptides of 68.5 and 69.3 kd, respectively. Primary sequence analysis, coupled with biochemical studies on the topology, indicates that both ribophorins are largely luminally disposed, spanning the membrane once and having 150 and 70 amino acid long cytoplasmically disposed C termini, respectively. Both are synthesized as precursors having cleavable signal sequences of 23 (ribophorin I) and 22 (ribophorin II) amino acids. The topology suggested by the primary structure has been confirmed biochemically using proteolytic enzymes and anti-ribophorin antibodies. Proteolysis of intact microsomes with a variety of enzymes resulted in a reduction in the apparent mol. wt of ribophorin I that would correspond to a loss of its 150-amino acid cytoplasmic tail. In the case of ribophorin II, it is completely resistant to such proteolysis which is consistent with its luminal disposition and fairly hydrophobic C terminus.(ABSTRACT TRUNCATED AT 250 WORDS)
Atlas of plant and animal histology
E ndoplasmic reticulum is a complex membrane-bound compartment arranged in tubules and flattened cisterns interconnected and sharing the same lumen (inner space) and membrane. Endoplasmic reticulum membrane is also continuous with the outer membrane of the nuclear envelope. Tubules and cisterns are distributed trough the cytoplasm from the nuclear envelope to close to the plasma membrane, so that they can account for half of the total cellular membranes. Endoplasmic reticulum membrane is thinner (around 5 nm in thickness) than other organelle membranes because they have lipids with shorter fatty acid chains.
E ndoplasmic reticulum membranes are organized in domains or regions that carry out different functions. At transmission electron microscopy, it is easy to distinguish two domains: rough and smooth endoplasmic reticulum (Figure 1). Rough endoplasmic reticulum membranes are arranged forming cisterns and more or less straight tubules, both having many ribosomes associated to their cysotolic membrane surface (that is why the name rough). Smooth endoplasmic reticulum is organized in irregular and convoluted tubules, with no associated ribosomes. The outer membrane of the nuclear envelope may regarded as part of the rough endoplasmic domain because it is physically continuous with the membranes of the rough endoplasmic tubules and it has many associated ribosomes doing translation.
Figure 1. Endoplasmic reticulum can be found all over the cytoplasm, from the nuclear envelope to the plasma membrane. Rough and smooth endoplasmic reticulum membranes are continuous. Rough endoplasmic reticulum is organized in cisterns and tubules that show associated ribosomes, whereas smooth endoplasmic reticulum is arranged in tubules with no ribosomes attached. The outer nucelar envelope membrane is continous with the endoplasmic reticulum membranes
R ough and smooth endoplasmic reticulum do not usually share the same cytosolic space. This non overlapping distribution is observed in hepatocytes, neurons and cells synthesizing steroid hormone. However, in some cytosolic regions there is not clear segregation between both domains, and tubules with associated ribosomes are intermingled with naked tubules. The spatial distribution of the endoplasmic reticulum through the cytosol is set by the cytoskeleton , mostly microtubules in animal cells, whereas actin filaments are the major responsible for the endoplasmic reticulum distribution in plant cells.
1. Rough endoplasmic reticulum
R ough endoplasmic reticulum is organized in more or less straight tubules and flattened cisternae . Sometimes, cisternae are tidily piled. The name "rough" comes from the electron microscopy images where ribosomes , black particles, are observed coating the endoplasmic reticulum membrane (Figure 2). The density of associated ribosomes influences the rough endoplasmic reticulum membranes organization, so that a high density causes a cistern-like morphology, whereas lower density is found in tubules. Cisternae and tubules coexist in the same cell, but those cells with an intense secretory activity show dense piles of cisternae, which means a highly developed rough endoplasmic reticulum.
Fiigure 2. Transmission electron microscopy image. Rough endoplasmic reticulum cisternae are observed, which extend from the nuclear envelope to the proximity of the plasma membrane. Ribosomes are observed as black dots associated to endoplasmic reticulum membranes. Note ribosomes associated to the outer membrane of the nuclear envelope as well.
P rotein synthesis is the main function of the rough endoplasmic reticulum. These proteins end up at different places , such as the extracellular space, plasma membrane, or at membranes and lumen of several organelles involved in the vesicular trafficking, such as Golgi apparatus, endosomes, and lysosomes. Many proteins will be part of the plasma membrane, and of other membranes, as transmembrane proteins. Furthermore, rough endoplasmic reticulum needs to synthesized proteins for itself, which are known as resident or constituent proteins . Keep in mind that each protein should "know" its correct destination in the cell. This can be accomplished by a signal peptide (short sequence of amino acids) or specific modifications of the protein, which work as postal addresses . For example, endoplasmic reticulum resident proteins contain a four amino acid sequence close to the end carboxyl group.
A lmost any protein targeted for secretion or being part of a compartment of the vesicular traffic begins to be synthesized in cytosolic free ribosomes , but the synthesis ends in the endoplasmic reticulum, leaving the protein either free in the lumen or as part of the reticulum membrane. The process of protein synthesis starts when an mRNA, which carries information for a protein of the vesicular trafficking, joins to a small ribosomal subunit, and then to a large ribosomal subunit, to begin the translation (Figure 3). The first translated segment of the mRNA is a sequence of amino acids known as signal peptide , which is about 70 amino acids long. This sequence is recognized by a cytosolic molecule referred as SRP (sequence recognition particle). SRP is a mix of 1 RNA and 6 polypeptides that joins to the signal peptide and slows vdown the translation process. The mRNA-ribosome-SRP-signal-peptide complex diffuses through the cytosol until it hits a rough endoplasmic reticulum membrane. In these membranes, there are SRP-receptors which recognize the SRP. The whole complex becomes attached to the membrane and then interacts with a translocon , a large transmembrane protein with a channel. Then, SRP and SRP-receptor are released and mRNA-ribosome-signal-peptide attached to the translocon can resume translation , but the nascent polypeptide grows now inside the translocon channel. The signal peptide gets fixed to the channel walls, while the rest of the protein is falling into the lumen of the endoplasmic reticulum cistern. The signal peptide is removed by a peptidase, and once completely translated, the new protein is released and remains free in the lumen, and quickly is folded to get a proper spatial conformation helped by chaperones, another type of proteins. When translation is finished, the ribosome-mRNA is disengaged from the translocon, and the three are free in the cytosol for another round .
Figure 3. Synthesis of soluble proteins that are released into the lumen of the endoplasmic reticulum.
T ransmembrane proteins contain sequences of hydrophobic amino acids. When these sequences are being translated and going through the translocon channel, they can cross the wall of the translocon and be among the fatty acid chains of membrane lipids. The process is rather complex and diverse depending on the protein. For example, some receptors are transmembrane proteins with a chain of amino acids that can cross seven times the cell membrane, by means of alternating hydrophobic and hydrophilic amino acid sequences. There are other proteins spanning just one monolayer of the membrane, and they have to be either in the cytosolic monolayer or in the monolayer facing the lumen. Although it is no common in animal cells, rough endoplasmic reticulum may import some proteins completely synthesized in the cytosol by a process known as posttranslational translocation, which is mediated by chaperones.
P roteins in the rough endoplasmic reticulum are modified while they are being synthesized. a) Asparagine amino acids are glycosysilated ( N-glycosylation ) with a molecular complex composed of 15 monosaccharides. This molecular complex is first assembled into a molecule of dolichol phosphate, a membrane lipid, and then is transferred to an asparagine of the nascent protein. In the Golgi apparatus, some terminal monosaccharides of this complex will be lost and other saccharides will be added. b) Some proteins, mostly those targeted to the extracellular matrix, are hydroxylated . In this way, proline and lysine amino acids of the collagen molecules end up being hydroxyproline and hydroxylysine amino acids. c) Some proteins of the plasma membrane are chemically bonded to some membrane lipids. This chemical bond is also established in the rough endoplasmic reticulum. d) Disulfide bonds between polypetide chains are also formed in endoplasmic reticulum.
Formación y fusión de vesículas. -->
A quality control of synthesized proteins occurs in the rough endoplasmic reticulum, so that those defective proteins are removed from the reticulum and degraded in the cytosol. Proteins known as chaperones , which are needed for a proper folding of newly synthesized proteins, also play an essential role in detecting defective proteins and labelling them for degradation. Other proteins bearing lectin domains are able to detect and recognize wrong arrangements of carbohydrates. Wrong folding of nascent proteins, which may lead to cell damages, is more frequent than one may imagine.
2. Smooth endoplasmic reticulum
S mooth endoplasmic reticulum is a network of interconnected tubules , which are continuous with the rough endoplasmic reticulum. There are no ribosomes associated to its membrane, therefore it is named smooth, and the majority of proteins in this compartment comes from the rough endoplasmic reticulum domain. Smooth endoplasmic reticulum is abundant in those cells involved in lipid metabolism or detoxification, and is also an organelle for calcium storage.
Salient functions of the smooth endoplasmic reticulum are:
M ost membrane lipids are assembled in the smooth endoplasmic reticulum, including glycerophospholipids and cholesterol. The components of the glycerophospholipids come from other parts of the cytoplasm and assembled in the membranes of the endoplasmic reticulum. Fatty acids are inserted in the cytosolic monolayer of the organelle membrane. Glycerophospholipid heads are then linked to these fatty acids. Most part of the sphingolipid synthesis, however, happens in the Golgi apparatus, but ceramide , the basic component of sphingolipids, is assembled in the smooth endoplasmic reticulum. Once glycerophospholipids and ceramide are complete assembled, they are initially located in the cytosolic monolayer of the endoplasmic reticulum membrane. Since flip-flop movement is nearly forbidden for lipids by the hydrophobic environment of fatty acid chains, lipids need help to be transferred to the other monolayer (that facing the lumen). There are specialized proteins that can move lipids from one monolayer to the other: flippases, floppases and scramblases.
Figure 4. Suggested ways for transferring lipids between cellular membranes: vesicular trafficking, carriers and membrane contacts.
T ransferring lipids between membranes is done by vesicles, molecular carriers and at membrane physical contac sites (Figure 4). Vesicles , through vesicular trafficking, transport in their membranes lipids synthesized in the endoplasmic reticulum to other organelles. Mitochondria, chloroplasts and peroxisomes are not part of the vesicular traffic, so some membrane lipids are synthesized locally, but many others are imported from the endoplasmic reticulum by molecular carriers . For example, glycerophospholipids are transported by a cytosolic protein known as glycerophospholipid interchanger. It can take a lipid from the membrane of the smooth endoplasmic reticulum and leaves it in the membrane of other organelle. Furthermore, many electron microscopy images show physical contacts between membranes of different organelles, for example between endoplasmic reticulum and mitochondria or peroxisomes. These contacts may facilitate interchange of lipids between different membranes. Chloroplasts can synthesize their own glycerophospholipids and glycolipids. However, endoplasmic reticulum membranes and chloroplast membranes are also observed very close to each other in electron microscopy images.
C holesterol is mostly synthesized in the smooth endoplasmic reticulum. It is an important molecule for membranes, particularly for the plasma membrane. Cholesterol is transported by vesicles and molecular carriers from the endoplasmic reticulum to the plasma membrane (Figure 4). In yeasts, that have ergosterol in their membranes instead of cholesterol, the main mechanism to move ergosterol from the endoplasmic reticulum to the plasma membrane is a diverse set of transporters. This transport does not need ATP.
T riacylglycerols are synthesized in the smooth endoplasmic reticulum. These lipids are stored in the reticulum itself or as lipid droplets . The synthesis of triacylglycerols is intense in adipocytes, the fat storing cells of animals. The overproduction of lipids is stored in cytoplasmic lipid droplets. This fat-storing organelle works as an energy source for the body when needed, and in some species for thermal insulation as well. Triacylglycerols are also part of the lipoproteins , and requiered for the production of steroid hormones and bile acids .
H epatocytes , the liver cells, show a highly developed smooth endoplasmic reticulum. In the smooth endoplasmic reticulum membranes, the P450 protein family is in charge of removing potentially toxic metabolites, as well as liposoluble toxins incorporated during the digestion. The shape of the smooth endoplasmic reticulum tubules, and the lack of ribosomes, allows a large surface of membrane related to the organelle volume. In addition, it is able to increase the length of the tubules to make room to all these enzymes, which in turn it depends on how many toxic substances the animal body contain.
Dephosphorylation of 6-phosphate glucose
G lucose is usually stored as glycogen, mainly in the liver. Two hormones regulate the glucose release from the liver to the blood: insulin and glucagon. Catabolism of glycogen produces 6-phosphate glucose, which cannot cross the cell membrane, and hence cannot leave the cell. Glucose 6-phosphatase , which is anchored to the endoplasmic reticulum, removes the phosphate residue allowing glucose to be moved out of the cell.
S mooth endoplasmic reticulum also works as a storage compartment for cytosolic calcium . Calcium is transported into the lumen by calcium pumps located in the organelle membrane. Calcium concentration in the smooth endoplasmic reticulum is in millimolar (mM), whereas in the cytosol is in nanomolar (nM). Stored calcium is released by extracellular and intracellular signals acting via second messengers, resulting in a cellular response, for example exocytosis. A remarkable example is the endoplasmic reticulum of the muscle cells (known as sarcoplasmic reticulum ) that captures and releases calcium to produce a cycle of muscle cell contraction and relaxation.
English AR, Zurek N, Voeltz GK. Peripheral ER structure and function. Current opinion in cell biology. 2009. 21:506-602.
Daleke DL. Phospholipid Flippases. The journal of biological chemistry. 2007. 282:821-825.
The sequence of DNA that encodes the sequence of the amino acids in a protein is transcribed into a messenger RNA chain. Ribosomes bind to messenger RNAs and use their sequences for determining the correct sequence of amino acids to generate a given protein. Amino acids are selected and carried to the ribosome by transfer RNA (tRNA) molecules, which enter the ribosome and bind to the messenger RNA chain via an anti-codon stem loop. For each coding triplet (codon) in the messenger RNA, there is a transfer RNA that matches and carries the correct amino acid for incorporating into a growing polypeptide chain. Once the protein is produced, it can then fold to produce a functional three-dimensional structure.
A ribosome is made from complexes of RNAs and proteins and is therefore a ribonucleoprotein complex. Each ribosome is composed of small (30S) and large (50S) components called subunits which are bound to each other:
- (30S) has mainly a decoding function and is also bound to the mRNA
- (50S) has mainly a catalytic function and is also bound to the aminoacylated tRNAs.
The synthesis of proteins from their building blocks takes place in four phases: initiation, elongation, termination, and recycling. The start codon in all mRNA molecules has the sequence AUG. The stop codon is one of UAA, UAG, or UGA since there are no tRNA molecules that recognize these codons, the ribosome recognizes that translation is complete.  When a ribosome finishes reading an mRNA molecule, the two subunits separate and are usually broken up but can be re-used. Ribosomes are ribozymes, because the catalytic peptidyl transferase activity that links amino acids together is performed by the ribosomal RNA. Ribosomes are often associated with the intracellular membranes that make up the rough endoplasmic reticulum.
Ribosomes from bacteria, archaea and eukaryotes in the three-domain system resemble each other to a remarkable degree, evidence of a common origin. They differ in their size, sequence, structure, and the ratio of protein to RNA. The differences in structure allow some antibiotics to kill bacteria by inhibiting their ribosomes, while leaving human ribosomes unaffected. In all species, more than one ribosome may move along a single mRNA chain at one time (as a polysome), each "reading" a specific sequence and producing a corresponding protein molecule.
The mitochondrial ribosomes of eukaryotic cells functionally resemble many features of those in bacteria, reflecting the likely evolutionary origin of mitochondria.  
Ribosomes were first observed in the mid-1950s by Romanian-American cell biologist George Emil Palade, using an electron microscope, as dense particles or granules.  The term "ribosome" was proposed by scientist Richard B. Roberts in the end of 1950s:
During the course of the symposium a semantic difficulty became apparent. To some of the participants, "microsomes" mean the ribonucleoprotein particles of the microsome fraction contaminated by other protein and lipid material to others, the microsomes consist of protein and lipid contaminated by particles. The phrase "microsomal particles" does not seem adequate, and "ribonucleoprotein particles of the microsome fraction" is much too awkward. During the meeting, the word "ribosome" was suggested, which has a very satisfactory name and a pleasant sound. The present confusion would be eliminated if "ribosome" were adopted to designate ribonucleoprotein particles in sizes ranging from 35 to 100S.
Albert Claude, Christian de Duve, and George Emil Palade were jointly awarded the Nobel Prize in Physiology or Medicine, in 1974, for the discovery of the ribosome.  The Nobel Prize in Chemistry 2009 was awarded to Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath for determining the detailed structure and mechanism of the ribosome. 
The ribosome is a complex cellular machine. It is largely made up of specialized RNA known as ribosomal RNA (rRNA) as well as dozens of distinct proteins (the exact number varies slightly between species). The ribosomal proteins and rRNAs are arranged into two distinct ribosomal pieces of different sizes, known generally as the large and small subunit of the ribosome. Ribosomes consist of two subunits that fit together (Figure 2) and work as one to translate the mRNA into a polypeptide chain during protein synthesis (Figure 1). Because they are formed from two subunits of non-equal size, they are slightly longer in the axis than in diameter.
Bacterial ribosomes Edit
Bacterial ribosomes are around 20 nm (200 Å) in diameter and are composed of 65% rRNA and 35% ribosomal proteins.  Eukaryotic ribosomes are between 25 and 30 nm (250–300 Å) in diameter with an rRNA-to-protein ratio that is close to 1.  Crystallographic work  has shown that there are no ribosomal proteins close to the reaction site for polypeptide synthesis. This suggests that the protein components of ribosomes do not directly participate in peptide bond formation catalysis, but rather that these proteins act as a scaffold that may enhance the ability of rRNA to synthesize protein (See: Ribozyme).
The ribosomal subunits of bacteria and eukaryotes are quite similar. 
The unit of measurement used to describe the ribosomal subunits and the rRNA fragments is the Svedberg unit, a measure of the rate of sedimentation in centrifugation rather than size. This accounts for why fragment names do not add up: for example, bacterial 70S ribosomes are made of 50S and 30S subunits.
Bacteria have 70S ribosomes, each consisting of a small (30S) and a large (50S) subunit. E. coli, for example, has a 16S RNA subunit (consisting of 1540 nucleotides) that is bound to 21 proteins. The large subunit is composed of a 5S RNA subunit (120 nucleotides), a 23S RNA subunit (2900 nucleotides) and 31 proteins. 
|70S||50S||23S (2904 nt)||31|
|5S (120 nt)|
|30S||16S (1542 nt)||21|
Affinity label for the tRNA binding sites on the E. coli ribosome allowed the identification of A and P site proteins most likely associated with the peptidyltransferase activity labelled proteins are L27, L14, L15, L16, L2 at least L27 is located at the donor site, as shown by E. Collatz and A.P. Czernilofsky.   Additional research has demonstrated that the S1 and S21 proteins, in association with the 3′-end of 16S ribosomal RNA, are involved in the initiation of translation. 
Archaeal ribosomes Edit
Archaeal ribosomes share the same general dimensions of bacteria ones, being a 70S ribosome made up from a 50S large subunit, a 30S small subunit, and containing three rRNA chains. However, on the sequence level, they are much closer to eukaryotic ones than to bacterial ones. Every extra ribosomal protein archaea have compared to bacteria has an eukaryotic counterpart, while no such relation applies between archaea and bacteria. 
Eukaryotic ribosomes Edit
Eukaryotes have 80S ribosomes located in their cytosol, each consisting of a small (40S) and large (60S) subunit. Their 40S subunit has an 18S RNA (1900 nucleotides) and 33 proteins.   The large subunit is composed of a 5S RNA (120 nucleotides), 28S RNA (4700 nucleotides), a 5.8S RNA (160 nucleotides) subunits and 46 proteins.   
|80S||60S||28S (4718 nt)||49|
|5.8S (160 nt)|
|5S (120 nt)|
|40S||18S (1874 nt)||33|
During 1977, Czernilofsky published research that used affinity labeling to identify tRNA-binding sites on rat liver ribosomes. Several proteins, including L32/33, L36, L21, L23, L28/29 and L13 were implicated as being at or near the peptidyl transferase center. 
Plastoribosomes and mitoribosomes Edit
In eukaryotes, ribosomes are present in mitochondria (sometimes called mitoribosomes) and in plastids such as chloroplasts (also called plastoribosomes). They also consist of large and small subunits bound together with proteins into one 70S particle.  These ribosomes are similar to those of bacteria and these organelles are thought to have originated as symbiotic bacteria  Of the two, chloroplastic ribosomes are closer to bacterial ones than mitochrondrial ones are. Many pieces of ribosomal RNA in the mitochrondria are shortened, and in the case of 5S rRNA, replaced by other structures in animals and fungi.  In particular, Leishmania tarentolae has a minimalized set of mitochondrial rRNA.  In contrast, plant mitoribosomes have both extended rRNA and additional proteins as compared to bacteria, in particular, many pentatricopetide repeat proteins. 
The cryptomonad and chlorarachniophyte algae may contain a nucleomorph that resembles a vestigial eukaryotic nucleus.  Eukaryotic 80S ribosomes may be present in the compartment containing the nucleomorph. [ citation needed ]
Making use of the differences Edit
The differences between the bacterial and eukaryotic ribosomes are exploited by pharmaceutical chemists to create antibiotics that can destroy a bacterial infection without harming the cells of the infected person. Due to the differences in their structures, the bacterial 70S ribosomes are vulnerable to these antibiotics while the eukaryotic 80S ribosomes are not.  Even though mitochondria possess ribosomes similar to the bacterial ones, mitochondria are not affected by these antibiotics because they are surrounded by a double membrane that does not easily admit these antibiotics into the organelle.  A noteworthy counterexample, however, includes the antineoplastic antibiotic chloramphenicol, which successfully inhibits bacterial 50S and eukaryotic mitochondrial 50S ribosomes.  The same of mitochondria cannot be said of chloroplasts, where antibiotic resistance in ribosomal proteins is a trait to be introduced as a marker in genetic engineering. 
Common properties Edit
The various ribosomes share a core structure, which is quite similar despite the large differences in size. Much of the RNA is highly organized into various tertiary structural motifs, for example pseudoknots that exhibit coaxial stacking. The extra RNA in the larger ribosomes is in several long continuous insertions,  such that they form loops out of the core structure without disrupting or changing it.  All of the catalytic activity of the ribosome is carried out by the RNA the proteins reside on the surface and seem to stabilize the structure. 
High-resolution structure Edit
The general molecular structure of the ribosome has been known since the early 1970s. In the early 2000s, the structure has been achieved at high resolutions, of the order of a few ångströms.
The first papers giving the structure of the ribosome at atomic resolution were published almost simultaneously in late 2000. The 50S (large prokaryotic) subunit was determined from the archaeon Haloarcula marismortui  and the bacterium Deinococcus radiodurans,  and the structure of the 30S subunit was determined from Thermus thermophilus.  These structural studies were awarded the Nobel Prize in Chemistry in 2009. In May 2001 these coordinates were used to reconstruct the entire T. thermophilus 70S particle at 5.5 Å resolution. 
Two papers were published in November 2005 with structures of the Escherichia coli 70S ribosome. The structures of a vacant ribosome were determined at 3.5 Å resolution using X-ray crystallography.  Then, two weeks later, a structure based on cryo-electron microscopy was published,  which depicts the ribosome at 11–15 Å resolution in the act of passing a newly synthesized protein strand into the protein-conducting channel.
The first atomic structures of the ribosome complexed with tRNA and mRNA molecules were solved by using X-ray crystallography by two groups independently, at 2.8 Å  and at 3.7 Å.  These structures allow one to see the details of interactions of the Thermus thermophilus ribosome with mRNA and with tRNAs bound at classical ribosomal sites. Interactions of the ribosome with long mRNAs containing Shine-Dalgarno sequences were visualized soon after that at 4.5–5.5 Å resolution. 
In 2011, the first complete atomic structure of the eukaryotic 80S ribosome from the yeast Saccharomyces cerevisiae was obtained by crystallography.  The model reveals the architecture of eukaryote-specific elements and their interaction with the universally conserved core. At the same time, the complete model of a eukaryotic 40S ribosomal structure in Tetrahymena thermophila was published and described the structure of the 40S subunit, as well as much about the 40S subunit's interaction with eIF1 during translation initiation.  Similarly, the eukaryotic 60S subunit structure was also determined from Tetrahymena thermophila in complex with eIF6. 
Ribosomes are minute particles consisting of RNA and associated proteins that function to synthesize proteins. Proteins are needed for many cellular functions such as repairing damage or directing chemical processes. Ribosomes can be found floating within the cytoplasm or attached to the endoplasmic reticulum. Their main function is to convert genetic code into an amino acid sequence and to build protein polymers from amino acid monomers.
Ribosomes act as catalysts in two extremely important biological processes called peptidyl transfer and peptidyl hydrolysis.  The "PT center is responsible for producing protein bonds during protein elongation". 
Ribosomes are the workplaces of protein biosynthesis, the process of translating mRNA into protein. The mRNA comprises a series of codons which are decoded by the ribosome so as to make the protein. Using the mRNA as a template, the ribosome traverses each codon (3 nucleotides) of the mRNA, pairing it with the appropriate amino acid provided by an aminoacyl-tRNA. Aminoacyl-tRNA contains a complementary anticodon on one end and the appropriate amino acid on the other. For fast and accurate recognition of the appropriate tRNA, the ribosome utilizes large conformational changes (conformational proofreading).  The small ribosomal subunit, typically bound to an aminoacyl-tRNA containing the first amino acid methionine, binds to an AUG codon on the mRNA and recruits the large ribosomal subunit. The ribosome contains three RNA binding sites, designated A, P and E. The A-site binds an aminoacyl-tRNA or termination release factors   the P-site binds a peptidyl-tRNA (a tRNA bound to the poly-peptide chain) and the E-site (exit) binds a free tRNA. Protein synthesis begins at a start codon AUG near the 5' end of the mRNA. mRNA binds to the P site of the ribosome first. The ribosome recognizes the start codon by using the Shine-Dalgarno sequence of the mRNA in prokaryotes and Kozak box in eukaryotes.
Although catalysis of the peptide bond involves the C2 hydroxyl of RNA's P-site adenosine in a proton shuttle mechanism, other steps in protein synthesis (such as translocation) are caused by changes in protein conformations. Since their catalytic core is made of RNA, ribosomes are classified as "ribozymes,"  and it is thought that they might be remnants of the RNA world. 
In Figure 5, both ribosomal subunits ( small and large ) assemble at the start codon (towards the 5' end of the mRNA). The ribosome uses tRNA that matches the current codon (triplet) on the mRNA to append an amino acid to the polypeptide chain. This is done for each triplet on the mRNA, while the ribosome moves towards the 3' end of the mRNA. Usually in bacterial cells, several ribosomes are working parallel on a single mRNA, forming what is called a polyribosome or polysome.
Cotranslational folding Edit
The ribosome is known to actively participate in the protein folding.   The structures obtained in this way are usually identical to the ones obtained during protein chemical refolding however, the pathways leading to the final product may be different.   In some cases, the ribosome is crucial in obtaining the functional protein form. For example, one of the possible mechanisms of folding of the deeply knotted proteins relies on the ribosome pushing the chain through the attached loop. 
Addition of translation-independent amino acids Edit
Presence of a ribosome quality control protein Rqc2 is associated with mRNA-independent protein elongation.   This elongation is a result of ribosomal addition (via tRNAs brought by Rqc2) of CAT tails: ribosomes extend the C-terminus of a stalled protein with random, translation-independent sequences of alanines and threonines.  
Ribosomes are classified as being either "free" or "membrane-bound".
Free and membrane-bound ribosomes differ only in their spatial distribution they are identical in structure. Whether the ribosome exists in a free or membrane-bound state depends on the presence of an ER-targeting signal sequence on the protein being synthesized, so an individual ribosome might be membrane-bound when it is making one protein, but free in the cytosol when it makes another protein.
Ribosomes are sometimes referred to as organelles, but the use of the term organelle is often restricted to describing sub-cellular components that include a phospholipid membrane, which ribosomes, being entirely particulate, do not. For this reason, ribosomes may sometimes be described as "non-membranous organelles".
Free ribosomes Edit
Free ribosomes can move about anywhere in the cytosol, but are excluded from the cell nucleus and other organelles. Proteins that are formed from free ribosomes are released into the cytosol and used within the cell. Since the cytosol contains high concentrations of glutathione and is, therefore, a reducing environment, proteins containing disulfide bonds, which are formed from oxidized cysteine residues, cannot be produced within it.
Membrane-bound ribosomes Edit
When a ribosome begins to synthesize proteins that are needed in some organelles, the ribosome making this protein can become "membrane-bound". In eukaryotic cells this happens in a region of the endoplasmic reticulum (ER) called the "rough ER". The newly produced polypeptide chains are inserted directly into the ER by the ribosome undertaking vectorial synthesis and are then transported to their destinations, through the secretory pathway. Bound ribosomes usually produce proteins that are used within the plasma membrane or are expelled from the cell via exocytosis. 
In bacterial cells, ribosomes are synthesized in the cytoplasm through the transcription of multiple ribosome gene operons. In eukaryotes, the process takes place both in the cell cytoplasm and in the nucleolus, which is a region within the cell nucleus. The assembly process involves the coordinated function of over 200 proteins in the synthesis and processing of the four rRNAs, as well as assembly of those rRNAs with the ribosomal proteins.
The ribosome may have first originated in an RNA world, appearing as a self-replicating complex that only later evolved the ability to synthesize proteins when amino acids began to appear.  Studies suggest that ancient ribosomes constructed solely of rRNA could have developed the ability to synthesize peptide bonds.    In addition, evidence strongly points to ancient ribosomes as self-replicating complexes, where the rRNA in the ribosomes had informational, structural, and catalytic purposes because it could have coded for tRNAs and proteins needed for ribosomal self-replication.  Hypothetical cellular organisms with self-replicating RNA but without DNA are called ribocytes (or ribocells).  
As amino acids gradually appeared in the RNA world under prebiotic conditions,   their interactions with catalytic RNA would increase both the range and efficiency of function of catalytic RNA molecules.  Thus, the driving force for the evolution of the ribosome from an ancient self-replicating machine into its current form as a translational machine may have been the selective pressure to incorporate proteins into the ribosome's self-replicating mechanisms, so as to increase its capacity for self-replication.   
Ribosomes are compositionally heterogeneous between species and even within the same cell, as evidenced by the existence of cytoplasmic and mitochondria ribosomes within the same eukaryotic cells. Certain researchers have suggested that heterogeneity in the composition of ribosomal proteins in mammals is important for gene regulation, i.e., the specialized ribosome hypothesis.   However, this hypothesis is controversial and the topic of ongoing research.  
Heterogeneity in ribosome composition was first proposed to be involved in translational control of protein synthesis by Vince Mauro and Gerald Edelman.  They proposed the ribosome filter hypothesis to explain the regulatory functions of ribosomes. Evidence has suggested that specialized ribosomes specific to different cell populations may affect how genes are translated.  Some ribosomal proteins exchange from the assembled complex with cytosolic copies  suggesting that the structure of the in vivo ribosome can be modified without synthesizing an entire new ribosome.
Certain ribosomal proteins are absolutely critical for cellular life while others are not. In budding yeast, 14/78 ribosomal proteins are non-essential for growth, while in humans this depends on the cell of study.  Other forms of heterogeneity include post-translational modifications to ribosomal proteins such as acetylation, methylation, and phosphorylation.  Arabidopsis,     Viral internal ribosome entry sites (IRESs) may mediate translations by compositionally distinct ribosomes. For example, 40S ribosomal units without eS25 in yeast and mammalian cells are unable to recruit the CrPV IGR IRES. 
Heterogeneity of ribosomal RNA modifications plays an important role in structural maintenance and/or function and most mRNA modifications are found in highly conserved regions.   The most common rRNA modifications are pseudouridylation and 2’-O methylation of ribose. 
Endoplasmic Reticulum: Rough and Smooth
This chapter discuses the morphology, biochemistry, and function of the endoplasmic reticulum (ER) in a variety of cell types. The ER maintains and generates its own membrane complex in addition to providing the components of membranes for other cellular compartments including plasma membrane, Golgi apparatus, lysosomes, and nuclear envelope. The location of the ER corresponds to the basophilic regions of the cell seen in the light microscope. The earliest observations of this organelle in thin sections described it as a continuous three-dimensional reticulum made up of a network of membrane-enclosed spaces in the form of tubules that were in continuity with the layers of flattened cisternae. The tubular elements free of ribosomes are referred to as smooth endoplasmic reticulum and the ribosome-studded component is called rough endoplasmic reticulum. Molecular genetics, monoclonal antibodies, in situ immunocytochemistry, complementary cDNA probes, as well as refinements in and development of new ultrastructural techniques, biochemical analyses, and laboratory equipment promise to greatly enhance current knowledge about the ER.
Protein targeting to the Endoplasmic Reticulum
1. Proteins entering the ER
|Overview: Synthesis of all proteins begins in the cytosol compartment. For proteins entering the secretory or Lysosomal pathways, the first step is targeting to the endoplasmic reticulum. This targeting relies on a targeting signal encoded in the N terminal portion of the protein. The targeting signal is recognized by a specific receptor that results in the protein entering the endoplasmic reticulum.|
1. Targeting of Proteins to the Endoplasmic Reticulum.
Synopsis. Synthesis of proteins entering the endoplasmic reticulum is initiated on free ribosomes. A targeting sequence of hydrophobic amino acids near the amino terminal end of the growing polypeptide results in the binding of the ribosome to ER membrane and in insertion of the polypeptide into the endoplasmic reticuluum.
Proteins secretory or lysosomal pathways enter the ER and don't come out again. The proteins entering either of these pathways may be of either of two types:
- Proteins that are completely translocated into the endoplasmic reticuluum. These proteins are soluble (not membrane proteins) and are destined for secretion, or for transfer to lysosomes. In all of these cases the proteins are never part of membranes.
- Proteins that are inserted into membranes, and hence are only partially translocated into the endoplasmic reticuluum. These proteins may be destined for ER, membranes of another organelle (Golgi, lysosomes or endosomes), or the plasma membrane. In all of these cases the proteins stay within the membrane once they are inserted into the ER membrane (e.g. cellulose synthase).
Translation of all proteins begins on free ribosomes. Those ribosomes that produce proteins for export through the endoplasmic reticulum become attached to the endoplasmic reticulum as ribosomes of the rough ER. The signal for ER entry is 8 or more hydrophobic amino acid residues (Table 14-3) which rivets the polypeptide to the ER membrane and is also involved in translocation.
Whether or not a ribosome becomes attached to the endoplasmic reticulum depends on the nature of the message being translated, the protein being made, and is not an intrinsic property of the ribosome itself. The ribosome and its attached nascent peptide become targeted to the endoplasmic reticulum.
Targeting to the endoplasmic reticulum takes place through the interaction of the signal peptide sequence ( a sequence of at least eight hydrophobic amino acids at the amino terminal end of the polypeptide. The emerging signal sequence combines with a 'signal recognition particle' (SRP). This greatly reduces the rate of translocation and allows the ribosome to attach to the endoplasm reticulum by means of a special SRP receptor in the ER membrane.
The ribosome becomes attached to a ribosome receptor that also functions as the translocation channel for the newly synthesized polypeptide. As the ribosome becomes attached, the SRP is removed and translation resumes.
Figure 14-13. shows two components.
1. There is a Signal Recognition Particle (SRP) in the cytosol. This binds to the ER Signal sequence when it is exposed on the ribosome and slows protein synthesis long enough to allow the SRP to find the second part, the SRP Receptor.
2. The Signal Recognition Particle Receptor (SRPR) which is embedded in the ER membrane. We now have the new polypeptide synthesizing system in place and protein synthesis speeds up. It seems that the Signal Sequence opens the translocation channel.
Experimental test that ER targeting signal is both necessary and sufficient to bring about targeting.
|Figure 14-6 experimental test of the role of signal sequences. IMPORTANT|
How do proteins get into the ER?
The peptide moves through the translocation channel into the lumen of the ER. The signal peptide sequence remains attached to the membrane. It is later cleaved off by a signal peptidase. Leaving the protein free in the lumen of the ER.
|Figure 14-14||Animation of this process|
Key point is that the orientation of a protein in the membrane is established when it is first inserted into the membrane. This orientation of the protein persists all of the way to its final destination. That is, the cytosolic side of membrane remains on the cytosolic side throughout all processes.
As membrane proteins are being translated, they are translocated or transferred into the ER until a hydrophobic membrane crossing domain is encountered. This serves as a 'stop transfer' signal and leaves the protein inserted in the ER membrane.
The hydrophobic trans-membrane domain holds the protein in the membrane because of the very strong hydrophobic interaction between this part of the protein and the hydrophobic membrane core.
Try this excellent link to web site dealing with insertion of proteins in membrane.
Proteins with multiple membrane crossing domains are inserted in the the membrane through the action of multiple pairs of start transfer and stop transfer signals:
There are two major categories of hydrophobic signals used in insertion of membrane proteins. All of these are membrane crossing domains:
- Start transfer sequences. These are of two types:
- N-terminal signal peptide sequence - a cluster of about 8 hydrophobic amino acids at the N-terminal end of a protein. This sequence remains in the membrane and is cleaved off of the protein after transfer through the membrane.
- Internal start transfer sequence. Similar to a signal sequence, but located internally (not at the N terminal end of the protein). It also binds to the SRP and initiates transfer. Unlike the N-terminal signal sequence, it is not cleaved after transfer of the protein.
This process of membrane insertion has a very important result: It establishes orientation of membrane proteins. Recall the earlier discussion of 'sidedness of membranes'. This is one of the chief ways that 'sidedness' happens.
Notice that the C-terminal end of the protein is on the cytosolic side of the membrane and the N-terminal end is not in the cytosol, but on the inside of the ER, or organelle.
This diagram shows the relation between translocation control sequences (signal sequences, start transfer sequences, stop transfer sequences) and the arrangement of the protein in the membrane. How would the translocation control sequences have to be arranged to get the N terminal end of the protein on the cytoplasmic side? - to get the C terminal end of the protein on the cytoplasmic side?
Now look at what happens if the protein is incorporated into a vesicle and later fused with the plasma membrane: The cytosolic side remains in the cytosol. This is a key idea.
Make a map of each of the proteins shown at A and B in the figure at the left. Indicate N terminal end, the relative location of any signal sequences. start transfer sequences, stop transfer sequences, and the C terminal end. The membrane crossing domains are shown in red.
Aside: On Collagen Pages 601-602
Just a word about the protein collagen, which may form more that 50% by weight of certain tissues in your body. This is an extracellular fibrillar polymer, which has some similar functions to cellulose in plants, but which is built of protein (not polysaccharide).
The textbook tells you some neat things about this molecule, which is neat especially if you are , for example, double-jointed.
The textbook does not tell you of the relevance to collagen to our present topic.
Collagen differs from other most other proteins, but is similar to a few others like keratin and elastin, because it contains two modified amino acids (hydroxyproline and hydroxylysine). Both of these amino acids are coded normally on the rough ER, as proline and lysine BUT as they are transferred to the ER, some of these amino acids are hydroxylated by an enzyme which is part of the translocation machinery in the ER membrane.
So, it is important to understand that translocation may also include modification. We believe that the signal for this is in the protein sequence, where pro-collagen contains many repeats Pro.Pro.Gly. and usually the first Pro is the one that is modified.
The translated sequence is 30% composed of pro pro gly with about 6% lys. As collagen is made and imported into the ER about 40% of the pro is hyrozylated to form 4 hydroxyproline. The enzyme involved is proline hydrozylase. This enzyme is located in the ER membrane, associated with RER. The resulting sequence in collagen is hyp pro gly some hydroxy lysine is formed also.
ER is a network of membranous sacs that form interconnected tubules, vesicles and cisternae. In 1945, Ernest Fullam, Keith Porter and Albert Claude were observed the endoplasmic reticulum. The ER membrane is a continuation of the outer nuclear membrane. The eukaryotic cells have ER. The ER membrane synthesizes all of the transmembrane proteins and lipids necessary for most of the cells’ organelles. They have several functions in the cell like protein synthesis, production of steroids, sequestration of calcium, and also storage and production of glycogen.
Most of the lipids for mitochondrial and peroxisomal membranes are also made by the ER membrane. The ER are of two types- rough ER and smooth ER. The rough ER contains ribosomes and hence appears rough whereas the smooth ER does not have ribosomes. The endoplasmic reticulum is a highly versatile organelle involved in synthesis and transport of proteins, glycoproteins, and lipoproteins synthesis of cholesterol, steroids, phospholipids, and triglycerides it participates in degradation of glycogen, and in the metabolism of xenobiotics.
The rough ER is associated with ribosomes which is the site protein synthesis. The ribosome free ER is known as smooth ER which is the centre of lipid and membrane protein synthesis.
Rough Endoplasmic Reticulum (RER)
RER is arranged as a series of stacked membranes close to the nucleus. They appear rough as there are large number of ribosome attached to the cytoplasmic side of their membranes. The ribosomes undergo the function of protein synthesis.
Regions of cytoplasmic matrix containing RER take basic stain due to the RNA content of ribosomes. These regions are known as cergastoplasm or basophilic bodies or chromophilic substances by early cytologists. In nerve cells such regions are called nissl bodies. In RER, ribosomes are often present as polysomes held together by mRNA.
Smooth Endoplasmic Reticulum (SER)
SER appear smooth as ribosomes are not attached to their walls. It occurs in cells involved in the metabolism of lipids and glycogen. Muscle cells have numerous SER and are known as sarcoplasmic reticulum. Smooth ER is also abundant in hepatocytes which is the principal site of production of lipoproteins which are carriers of lipids to various parts of the body through the bloodstream. The SER consists of tubules and vesicles that forming a network, which increased surface area for the action and storage of key enzymes and the product of these enzymes.
Sarcoplasmic reticulum is a type of smooth ER found in smooth and striated muscles. The SER synthesizes molecules while the SR stores and pumps calcium ions. Calcium was stored in the SR, which it sequesters and then releases when the muscle cell is stimulated. The release of calcium by SR during electrical stimulation of the cell plays a important role in excitation-contraction coupling.
Functions of ER
The functions of SER include steroid metabolism, regulation of calcium concentration, metabolism of carbohydrates, synthesis of lipids and steroids, drug detoxification. The enzyme glucose-6-phosphatasepresentin SER which converts glucose-6-phosphate to glucose, which is a step in gluconeogenesis.
ER also contains enzymes that catalyze the detoxification of certain drugs and harmful substances produced by metabolism.
ER also serves as an intracellular Ca 2+ store which are used in many cell signaling processes. Sarcoplasmic reticulum in muscle cells are also specialized in Ca 2+ storage.
What is Endoplasmic Reticulum
Endoplasmic reticulum (ER), which is an organelle found in eukaryotes, contains flattened membranous sacs, interconnected with each other. These sacs are tube-like structures, which are called cisternae. Cisternae are held together by the cytoskeleton of the cell. Two types of ER is found: smooth ER and rough ER. Only rough ER contains bound ribosomes to the membrane of the ER. Smooth ER is involved in the lipid metabolism. Rough ER provides sites for protein synthesis.
Two fractions of rough endoplasmic reticulum from rat liver. I. Recovery of rapidly sedimenting endoplasmic reticulum in association with mitochondria
Low-speed centrifugation (640 g) of rat liver homogenates, prepared with a standard ionic medium, yielded a pellet from which a rapidly sedimenting fraction of rough endoplasmic reticulum (RSER) was recovered free of nuclei. This fraction contained 20-25% of cellular RNA and approximately 30% of total glucose-6-phosphatase (ER marker) activity. A major portion of total cytochrome c oxidase (mitochondrial marker) activity was also recovered in this fraction, with the remainder sedimenting between 640 and 6,000 g. Evidence is provided which indicates that RSER may be intimately associated with mitochondria. Complete dissociation of ER from mitochondria in the RSER fraction required very harsh conditions. Sucrose density gradient centrifugation analysis revealed that 95% dissociation could be achieved when the RSER fraction was first resuspended in buffer containing 500 mM KCl and 20 mM EDTA, and subjected to shearing. Excluding KCl, EDTA, or shearing from the procedure resulted in incomplete separation. Both electron microscopy and marker enzyme analysis of mitochondria purified by this procedure indicated that some structural damage and leakage of proteins from matrix and intermembrane compartments had occurred. Nevertheless, when mitochondria from RSER and postnuclear 6,000-g pellet fractions were purified in this way fromanimals injected with [35S]methionine +/- cycloheximide, mitochondria from the postnuclear 6,000-g pellet were found to incorporate approximately two times more cytoplasmically synthesized radioactive protein per milligram mitochondrial protein (or per unit cytochrome c oxidase activity) than did mitochondria from the RSER fraction. Mitochondria-RSER associations, therefore, do not appear to facilitate enhanced incorporation of mitochondrial proteins which are newly synthesized in the cytoplasm.
Watch the video: RNA δομή, τύποι και λειτουργίες (November 2021).