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Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link
amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ami ...
together in the order specified by the
codon The genetic code is the set of rules used by living cell (biology), cells to Translation (biology), translate information encoded within genetic material (DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accom ...
s of
messenger RNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
(mRNA) molecules to form
polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called Protein, proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapepti ...
chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA (rRNA) molecules and many
ribosomal protein A ribosomal protein (r-protein or rProtein) is any of the proteins that, in conjunction with Ribosomal RNA, rRNA, make up the Ribosome, ribosomal subunits involved in the cellular process of translation (genetics), translation. ''E. coli'', other ...
s (RPs or r-proteins). The ribosomes and associated molecules are also known as the ''translational apparatus''.


Overview

The sequence of DNA that encodes the sequence of the
amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ami ...
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 The genetic code is the set of rules used by living cell (biology), cells to Translation (biology), translate information encoded within genetic material (DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accom ...
) in the messenger RNA, there is a unique transfer RNA that must have the exact anti-codon match, and carries the correct amino acid for incorporating into a growing
polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called Protein, proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapepti ...
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 (30 S) and large (50 S) 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
ribozyme Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonst ...
s, 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 The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ...
. Ribosomes from
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometre The micrometre (Amer ...
,
archaea Archaea ( ; singular archaeon ) is a Domain (biology), domain of Unicellular organism, single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially Taxonomy (biology), classified as bacter ...
and
eukaryote Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the ...
s 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
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...
s 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 A polyribosome (or polysome or ergosome) is a group of ribosomes bound to an Messenger RNA, mRNA molecule like “beads” on a “thread”. It consists of a complex of an mRNA molecule and two or more ribosomes that act to translation (biology) ...
), each "reading" a specific sequence and producing a corresponding protein molecule. The
mitochondrial ribosome The mitochondrial ribosome, or mitoribosome, is a Protein complexes, protein complex that is active in mitochondria and functions as a Ribosomal protein, riboprotein for Translation (biology), translating mitochondrial mRNAs encoded in mtDNA. The ...
s of eukaryotic cells 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-American cell biologist George Emil Palade, using an
electron microscope An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
, as dense particles or granules. They were initially called Palade granules due to their granular structure. The term "ribosome" was proposed in 1958:
Albert Claude Albert Claude (; 24 August 1899 – 22 May 1983) was a Belgium, Belgian-United States, American cell biologist and medical doctor who shared the Nobel Prize in Physiology or Medicine in 1974 with Christian de Duve and George Emil Palade. His elem ...
,
Christian de Duve Christian René Marie Joseph, Viscount de Duve (2 October 1917 – 4 May 2013) was a Nobel Prize-winning Belgian cytologist and biochemist Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemica ...
, and George Emil Palade were jointly awarded the
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute, Nobel Assembly at the Karolinska Institutet, Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Pr ...
, in 1974, for the discovery of the ribosome. The
Nobel Prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel#Nobel Prize, Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest ben ...
in
Chemistry Chemistry is the scientific study of the properties and behavior of matter. It is a natural science that covers the elements that make up matter to the compounds made of atoms, molecules and ions: their composition, structure, properties ...
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 complex cellular machine. It is largely made up of specialized RNA known as
ribosomal RNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal ...
(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.


Prokaryotic ribosomes

Prokaryotic ribosomes are around 20  nm (200  Å) in diameter and are composed of 65% rRNA and 35%
ribosomal protein A ribosomal protein (r-protein or rProtein) is any of the proteins that, in conjunction with Ribosomal RNA, rRNA, make up the Ribosome, ribosomal subunits involved in the cellular process of translation (genetics), translation. ''E. coli'', other ...
s. 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 Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonst ...
). The ribosomal subunits of
prokaryote A prokaryote () is a Unicellular organism, single-celled organism that lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek language, Greek wikt:πρό#Ancient Greek, πρό (, 'before') a ...
s and
eukaryote Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the ...
s 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 Sedimentation is the deposition of sediments. It takes place when particle (ecology), particles in Suspension (chemistry), suspension settle out of the fluid in which they are Entrainment (engineering), entrained and come to rest against a barr ...
in
centrifugation Centrifugation is a mechanical process which involves the use of the centrifugal force to separate particles from a solution according to their size, shape, density, medium viscosity and rotor speed. The denser components of the mixture migrate ...
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. Prokaryotes have 70 S 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
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabo ...
s. : 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

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 a eukaryotic counterpart, while no such relation applies between archaea and bacteria.


Eukaryotic ribosomes

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 49 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.


Plastoribosomes and mitoribosomes

In eukaryotes, ribosomes are present in
mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which i ...
(sometimes called mitoribosomes) and in
plastid The plastid (Greek: πλαστός; plastós: formed, molded – plural plastids) is a membrane-bound organelle found in the cells of plants Plants are predominantly Photosynthesis, photosynthetic eukaryotes of the Kingdom (biology), kingd ...
s such as
chloroplast A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, ...
s (also called plastoribosomes). They also consist of large and small subunits bound together with
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabo ...
s 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.


Making use of the differences

The differences between the bacterial and eukaryotic ribosomes are exploited by pharmaceutical chemists to create
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...
s 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 A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which i ...
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 In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to the ...
. A noteworthy counterexample, however, includes the antineoplastic antibiotic chloramphenicol, which successfully inhibits bacterial 50S and eukaryotic mitochondrial 50S ribosomes. Ribosomes in chloroplasts, however, are different: Antibiotic resistance in chloroplast ribosomal proteins is a trait that has to be introduced as a marker, with genetic engineering.


Common properties

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

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 ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative bacteria, Gram-negative, Facultative anaerobic organism, facultative anaer ...
'' 70S ribosome. The structures of a vacant ribosome were determined at 3.5  Å resolution using
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract into many specific directions. By measurin ...
. 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 Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the Messenger RNA, mRNA a ...
and
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
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 In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
and with
tRNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the Messenger RNA, mRNA a ...
s 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 ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
'' 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 ''Tetrahymena thermophila'' is a species of Ciliate, Ciliophora in the family Tetrahymenidae. It is a free living protozoa and occurs in fresh water. There is little information on the ecology and natural history of this species, but it is the ...
'' 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 ''Tetrahymena thermophila'' is a species of Ciliate, Ciliophora in the family Tetrahymenidae. It is a free living protozoa and occurs in fresh water. There is little information on the ecology and natural history of this species, but it is the ...
'' in complex with eIF6.


Function

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 The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough 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". In summary, ribosomes have two main functions: Decoding the message, and the formation of peptide bonds. These two functions reside in the ribosomal subunits. Each subunit is made of one or more rRNAs and many r-proteins. The small subunit (30S in bacteria and archaea, 40S in eukaryotes) has the decoding function, whereas the large subunit (50S in bacteria and archaea, 60S in eukaryotes) catalyzes the formation of peptide bonds, referred to as the peptidyl-transferase activity. The bacterial (and archaeal) small subunit contains the 16S rRNA and 21 r-proteins (''Escherichia coli''), whereas the eukaryotic small subunit contains the 18S rRNA and 32 r-proteins (Saccharomyces cerevisiae; although the numbers vary between species). The bacterial large subunit contains the 5S and 23S rRNAs and 34 r-proteins (''E. coli''), with the eukaryotic large subunit containing the 5S, 5.8S, and 25S / 28S rRNAs and 46 r-proteins (''S. cerevisiae''; again, the exact numbers vary between species).


Translation

Ribosomes are the workplaces of
protein biosynthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
, the process of translating
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
into
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabo ...
. The mRNA comprises a series of
codon The genetic code is the set of rules used by living cell (biology), cells to Translation (biology), translate information encoded within genetic material (DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accom ...
s which are decoded by the ribosome so as to make the protein. Using the mRNA as a template, the ribosome traverses each codon (3 
nucleotide Nucleotides are Organic compound, organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential ...
s) of the mRNA, pairing it with the appropriate amino acid provided by an aminoacyl-tRNA. Aminoacyl-tRNA contains a complementary
anticodon Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the Messenger RNA, mRNA a ...
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 Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical rol ...
, 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 The start codon is the first codon of a messenger RNA (mRNA) transcript translated by a ribosome. The start codon always codes for methionine in eukaryotes and Archaea and a N-formylmethionine N-Formylmethionine, (fMet) in bacteria, mitochondria a ...
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 In organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that c ...
involves the C2
hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom Chemical bond, covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or ...
of RNA's P-site
adenosine Adenosine (nucleoside#List of nucleosides and corresponding nucleobases, symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glyc ...
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 "
ribozyme Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonst ...
s," and it is thought that they might be remnants of the
RNA world The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replication, self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posi ...
. In Figure 5, both ribosomal subunits (small and large) assemble at the start codon (towards the 5' end of the
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
). The ribosome uses
tRNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the Messenger RNA, mRNA a ...
that matches the current codon (triplet) on the mRNA to append an
amino acid Amino acids are organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon chemical bond, bonds. Due to carbon's ability to Catenation, catenate (form chains with ot ...
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 A polyribosome (or polysome or ergosome) is a group of ribosomes bound to an Messenger RNA, mRNA molecule like “beads” on a “thread”. It consists of a complex of an mRNA molecule and two or more ribosomes that act to translation (biology) ...
''.


Cotranslational folding

The ribosome is known to actively participate in the
protein folding Protein folding is the physical process by which a protein chain is Translation (biology), translated to its native protein tertiary structure, three-dimensional structure, typically a "folded" Protein structure, conformation by which the prote ...
. 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 protein Knotted proteins are proteins whose backbones entangle themselves in a knot. One can imagine pulling a protein chain from both termini, as though pulling a string from both ends. When a knotted protein is “pulled” from both termini, it does not ...
s relies on the ribosome pushing the chain through the attached loop.


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 ''a''lanines and ''t''hreonines.


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
organelle In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to the ...
s, 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 The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cell (biology), cells (Fluid compartments#Intracellular compartment, intracellular fluid (ICF)). It is separated into compartments by membranes. For ...
, but are excluded from the
cell nucleus The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as ma ...
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 Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important Cell (biology), cellular components caused by sources such as reactive oxygen species, free ...
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 Exocytosis () is a form of active transport and solvent drag, bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell (''wikt:ex-#Prefix, exo-'' + ''cytosis''). As an active transport mechanism, ...
''.


Biogenesis

In bacterial cells, ribosomes are synthesized in the cytoplasm through the
transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...
of multiple ribosome gene
operon In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter (genetics), promoter. The genes are transcription (biology), transcribed together into an Messenger RNA, mRNA strand and eith ...
s. In eukaryotes, the process takes place both in the cell cytoplasm and in the nucleolus, which is a region within the
cell nucleus The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as ma ...
. 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.


Origin

The ribosome may have first originated in an
RNA world The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replication, self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posi ...
, appearing as a self-replicating complex that only later evolved the ability to synthesize proteins when
amino acid Amino acids are organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon chemical bond, bonds. Due to carbon's ability to Catenation, catenate (form chains with ot ...
s began to appear. Studies suggest that ancient ribosomes constructed solely of
rRNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal ...
could have developed the ability to synthesize
peptide bond In organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that c ...
s. 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 A self-replicating machine is a type of autonomous robot that is capable of reproducing itself autonomously using raw materials found in the environment, thus exhibiting self-replication in a way analogous to that found in nature. The concept of ...
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.


Heterogeneous ribosomes

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
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cell (biology), cells (Fluid compartments#Intracellular compartment, intracellular fluid (ICF)). It is separated into compartments by membranes. For ...
ic 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 a significant 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.


See also

* Aminoglycosides * Biological machines *
Posttranslational modification Post-translational modification (PTM) is the covalent and generally enzyme, enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by r ...
*
Protein dynamics Proteins are generally thought to adopt unique structures determined by their amino acid sequences. However, proteins are not strictly static objects, but rather populate ensembles of (sometimes similar) conformations. Transitions between these stat ...
* RNA tertiary structure *
Translation (genetics) In molecular biology and genetics, translation is the process in which ribosomes in the cytoplasm or endoplasmic reticulum synthesize proteins after the process of transcription (biology), transcription of DNA to RNA in the cell's nucleus ( ...
*
Wobble base pair A wobble base pair is a pairing between two nucleotides in RNA molecules that does not follow Watson-Crick base pair rules. The four main wobble base pairs are guanine-uracil (G-U), hypoxanthine-uracil (I-U), hypoxanthine-adenine (I-A), and hypox ...
* Ada Yonath—Israeli crystallographer known for her pioneering work on the structure of the ribosome, for which she won the
Nobel Prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel#Nobel Prize, Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest ben ...
.


References


External links


Lab computer simulates ribosome in motion


Gwen V. Childs, copie


Ribosome
i
''Proteopedia''
The free, collaborative 3D encyclopedia of proteins & other molecules
Ribosomal proteins families in ExPASy

© RCSB Protein Data Bank
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3D electron microscopy structures of ribosomes at the EM Data Bank (EMDB)
* {{Authority control Ribozymes Protein biosynthesis