Ribosome
The ribosome (/ˈraɪbəˌsoʊm, -boʊ-/) is a complex molecular machine, found within all living cells, that serves as the site of biological protein synthesis (translation). Ribosomes link amino acids together in the order specified by messenger RNA (mRNA) molecules. Ribosomes consist of two major components: the small ribosomal subunit, which reads the RNA, and the large subunit, which joins amino acids to form a polypeptide chain. Each subunit is composed of one or more ribosomal RNA (rRNA) molecules and a variety of ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.
The ribosome (/ˈraɪbəˌsoʊm, -boʊ-/) is a complex molecular machine, found within all living cells, that serves as the site of biological protein synthesis (translation). Ribosomes link amino acids together in the order specified by messenger RNA (mRNA) molecules. Ribosomes consist of two major components: the small ribosomal subunit, which reads the RNA, and the large subunit, which joins amino acids to form a polypeptide chain. Each subunit is composed of one or more ribosomal RNA (rRNA) molecules and a variety of ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.
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| Fig 1 ribosome |
Overview
The sequence of DNA, which encodes the sequence of the amino acids in a protein, is copied into a messenger RNA chain. It may be copied many times into RNA chains. Ribosomes can bind to a messenger RNA chain and use its sequence for determining the correct sequence of amino acids. Amino acids are selected, collected, and carried to the ribosome by transfer RNA (tRNA) molecules, which enter one part of the ribosome and bind to the messenger RNA chain. It is during this binding that the correct translation of nucleic acid sequence to amino acid sequence occurs. For each coding triplet in the messenger RNA there is a distinct transfer RNA that matches and which carries the correct amino acid for that coding triplet. The attached amino acids are then linked together by another part of the ribosome. Once the protein is produced, it can then fold to produce a specific functional three-dimensional structure although during synthesis some proteins start folding into their correct form.
A ribosome is made from complexes of RNAs and proteins and is therefore a ribonucleoprotein. Each ribosome is divided into two subunits: 1; a smaller subunit which binds to a larger subunit and the mRNA pattern, and 2; a larger subunit which binds to the tRNA, the amino acids, and the smaller subunit. When a ribosome finishes reading an mRNA molecule, these two subunits split apart. 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 bacteria and archaea, more than one ribosome may move along a single mRNA chain at one time, each "reading" its sequence and producing a corresponding protein molecule.
The mitochondrial ribosomes of eukaryotic cells, are produced from mitochondrial genes, and functionally resemble many features of those in bacteria, reflecting the likely evolutionary origin of mitochondria.
Discovery
Ribosomes were first observed in the mid-1950s by Romanian 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 1958:
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.
Structure
The ribosome is a highly 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 size, 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.
Prokaryotic 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 proves that the protein components of ribosomes do not directly participate in peptide bond formation catalysis, but rather suggests that these proteins act as a scaffold that may enhance the ability of rRNA to synthesize protein (See: Ribozyme).
The ribosomal subunits of prokaryotes 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, prokaryotic 70S ribosomes are made of 50S and 30S subunits.
Prokaryotes have 70S ribosomes, each consisting of a small (30S) and a large (50S) subunit. Their small subunit has a 16S RNA subunit (consisting of 1540 nucleotides) 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. 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.
Eukaryotes have 80S ribosomes, 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. 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.
The ribosomes found in chloroplasts and mitochondria of eukaryotes also consist of large and small subunits bound together with proteins into one 70S particle. These organelles are believed to be descendants of bacteria (see Endosymbiotic theory) and, as such, their ribosomes are similar to those of bacteria.
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.
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.
High-resolution structure
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 Å.
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 11–15Å 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- to 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.
Function
Ribosomes are organelles that 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.
Translation
Ribosomes are the workplaces of protein biosynthesis, the process of translating mRNA into protein. The mRNA comprises a series of codons that dictate to the ribosome the sequence of the amino acids needed 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 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; the P site binds a peptidyl-tRNA (a tRNA bound to the peptide being synthesized); and the E site binds a free tRNA before it exits the ribosome. 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 is able to identify the start codon by use of 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 RNA). The ribosome uses RNA 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 RNA, while the ribosome moves towards the 3' end of the mRNA. Usually in bacterial cells, several ribosomes are working parallel on a single RNA, forming what is called a polyribosome or polysome.
Addition of translation-independent amino acids
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.
Ribosome locations
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
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
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.
References
1. wikipedia free encyclopedia
2.Molecular Biology of the Cell
Bruce Alberts, University of California, San Francisco, USA
Alexander Johnson, University of California, San Francisco, USA
Julian Lewis, (Deceased), formerly of Cancer Research UK
David Morgan, University of California, San Francisco, USA
Martin Raff, University College London, UK
Keith Roberts, Emeritus, University of East Anglia, UK
Peter Walter, University of California, San Francisco, USA
- Publisher: Garland Science; 6 edition (2 December 2014)
- Language: English
- ISBN-10: 0815344643
- ISBN-13: 978-0815344643
3. CELL BIOLOGY by Dr CB POWER
- Publisher: Himalaya Publishing House (2010)
- Language: English
- ISBN-10: 9350246694
- ISBN-13: 978-9350246696
- ASIN: B003WWDSPC
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