Ribosomes
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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 am ...
together in the order specified by the codons 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 synthesizing a protein. mRNA is created during the p ...
(mRNA) molecules to form polypeptide 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 rRNA, make up the ribosomal subunits involved in the cellular process of translation. ''E. coli'', other bacteria and Archaea have a 30S small subunit an ...
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 am ...
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 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 ...
stem loop. For each coding triplet ( codon) 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 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 Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
peptidyl transferase The peptidyl transferase is an aminoacyltransferase () as well as the primary enzymatic function of the ribosome, which forms peptide bonds between adjacent amino acids using tRNAs during the translation process of protein biosynthesis. The subs ...
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 micrometres in length, bacteria were among ...
,
archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
and
eukaryote Eukaryotes () are organisms whose cells have a 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 three domains of life. Bacte ...
s in the
three-domain system The three-domain system is a biological classification introduced by Carl Woese, Otto Kandler, and Mark Wheelis in 1990 that divides cellular life forms into three domains, namely Archaea, Bacteria, and Eukaryota or Eukarya. The key difference fr ...
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 bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
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 mRNA molecule like “beads” on a “thread”. It consists of a complex of an mRNA molecule and two or more ribosomes that act to translate mRNA instructions into pol ...
), each "reading" a specific sequence and producing a corresponding protein molecule. The
mitochondrial ribosome The mitochondrial ribosome, or mitoribosome, is a protein complex that is active in mitochondria and functions as a riboprotein for translating mitochondrial mRNAs encoded in mtDNA. The mitoribosome is attached to the inner mitochondrial membrane ...
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 Romanian Americans are Americans who have Romanian ancestry. According to the 2017 American Community Survey, 478,278 Americans indicated Romanian as their first or second ancestry, however other sources provide higher estimates, which are most ...
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 Belgian-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 elementary education s ...
,
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. He made serendipitous discoveries of two cell organelles, peroxisome and lysosome, for which he shared ...
, 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 for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
, 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's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
in
Chemistry Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science that covers the Chemical element, elements that make up matter to the chemical compound, compounds made of atoms, molecules and ions ...
2009 was awarded to
Venkatraman Ramakrishnan Venkatraman Ramakrishnan (born 1952) is an Indian-born British and American structural biologist who shared the 2009 Nobel Prize in Chemistry with Thomas A. Steitz and Ada Yonath, "for studies of the structure and function of the ribosome" ...
, Thomas A. Steitz and
Ada E. Yonath Ada E. Yonath ( he, עדה יונת, ; born 22 June 1939) is an Israeli crystallographer best known for her pioneering work on the structure of ribosomes. She is the current director of the Helen and Milton A. Kimmelman Center for Biomolecular ...
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 rRNA, make up the ribosomal subunits involved in the cellular process of translation. ''E. coli'', other bacteria and Archaea have a 30S small subunit an ...
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 Crystallography is the experimental science of determining the arrangement of atoms in crystalline solids. Crystallography is a fundamental subject in the fields of materials science and solid-state physics ( condensed matter physics). The w ...
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 single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
s and
eukaryote Eukaryotes () are organisms whose cells have a 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 three domains of life. Bacte ...
s are quite similar. The unit of measurement used to describe the ribosomal subunits and the rRNA fragments is the
Svedberg A Svedberg unit or svedberg (symbol S, sometimes Sv) is a non- SI metric unit for sedimentation coefficients. The Svedberg unit offers a measure of a particle's size indirectly based on its sedimentation rate under acceleration (i.e. how fast a ...
unit, a measure of the rate of
sedimentation Sedimentation is the deposition of sediments. It takes place when particles in suspension settle out of the fluid in which they are entrained and come to rest against a barrier. This is due to their motion through the fluid in response to the ...
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 The prokaryotic small ribosomal subunit, or 30 S subunit, is the smaller subunit of the 70S ribosome found in prokaryotes. It is a complex of the 16S ribosomal RNA (rRNA) and 19 proteins. This complex is implicated in the binding of transfer ...
) 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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
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 label Affinity labels are a class of enzyme inhibitors that covalently bind to their target causing its inactivation. The hallmark of an affinity label is the use of a targeting moiety to specifically and reversibly deliver a weakly reactive group to the ...
ing 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 The peptidyl transferase is an aminoacyltransferase () as well as the primary enzymatic function of the ribosome, which forms peptide bonds between adjacent amino acids using tRNAs during the translation process of protein biosynthesis. The subs ...
center.


Plastoribosomes and mitoribosomes

In eukaryotes, ribosomes are present in
mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
(sometimes called mitoribosomes) and in
plastid The plastid (Greek: πλαστός; plastós: formed, molded – plural plastids) is a membrane-bound organelle found in the Cell (biology), cells of plants, algae, and some other eukaryotic organisms. They are considered to be intracellular endosy ...
s such as
chloroplast A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant and algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, and stores it in ...
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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
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 The cryptomonads (or cryptophytes) are a group of algae, most of which have plastids. They are common in freshwater, and also occur in marine and brackish habitats. Each cell is around 10–50 μm in size and flattened in shape, with an anteri ...
and
chlorarachniophyte The chlorarachniophytes are a small group of exclusively marine algae widely distributed in tropical and temperate waters. They are typically mixotrophic, ingesting bacteria and smaller protists as well as conducting photosynthesis. Normally the ...
algae may contain a
nucleomorph Nucleomorphs are small, vestigial eukaryotic nuclei found between the inner and outer pairs of membranes in certain plastids. They are thought to be vestiges of primitive red and green algal nuclei that were engulfed by a larger eukaryote. Becaus ...
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 bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
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 Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
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, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' 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 Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
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 Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
; 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
ångström The angstromEntry "angstrom" in the Oxford online dictionary. Retrieved on 2019-03-02 from https://en.oxforddictionaries.com/definition/angstrom.Entry "angstrom" in the Merriam-Webster online dictionary. Retrieved on 2019-03-02 from https://www.m ...
s. 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 Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebact ...
''Haloarcula marismortui'' and the bacterium ''
Deinococcus radiodurans ''Deinococcus radiodurans'' is an extremophilic bacterium and one of the most radiation-resistant organisms known. It can survive cold, dehydration, vacuum, and acid, and therefore is known as a polyextremophile. It has been listed as the world ...
'', and the structure of the 30S subunit was determined from ''
Thermus thermophilus ''Thermus thermophilus'' is a Gram-negative bacterium used in a range of biotechnological applications, including as a model organism for genetic manipulation, structural genomics, and systems biology. The bacterium is extremely thermophilic, w ...
''. 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, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'' 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 diffract into many specific directions. By measuring the angles ...
. Then, two weeks later, a structure based on
cryo-electron microscopy Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample s ...
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 mRNA and the amino ac ...
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 ''Thermus thermophilus'' is a Gram-negative bacterium used in a range of biotechnological applications, including as a model organism for genetic manipulation, structural genomics, and systems biology. The bacterium is extremely thermophilic, w ...
'' 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 mRNA and the amino ac ...
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 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 most wi ...
'' 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 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 most wi ...
'' in complex with
eIF6 Eukaryotic translation initiation factor 6 (EIF6), also known as Integrin beta 4 binding protein (ITGB4BP), is a human gene. Hemidesmosomes are structures which link the basal lamina to the intermediate filament cytoskeleton. An important functio ...
.


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. 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 cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical ...
, 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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
. 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 
nucleotide Nucleotides are 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 biomolecules wi ...
s) of the mRNA, pairing it with the appropriate amino acid provided by an
aminoacyl-tRNA Aminoacyl-tRNA (also aa-tRNA or charged tRNA) is tRNA to which its cognate amino acid is chemically bonded (charged). The aa-tRNA, along with particular elongation factors, deliver the amino acid to the ribosome for incorporation into the polypept ...
. 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 mRNA and the amino ...
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 Conformational proofreading or conformational selection is a general mechanism of molecular recognition systems in which introducing a structural mismatch between a molecular recognizer and its target, or an energetic barrier, enhances the recogn ...
). 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 ro ...
, 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 The A-site (A for aminoacyl) of a ribosome is a binding site for charged t-RNA molecules during protein synthesis. One of three such binding sites, the A-site is the first location the t-RNA binds during the protein synthesis process, the other ...
binds an aminoacyl-tRNA or termination release factors; the
P-site The P-site (for peptidyl) is the second binding site for tRNA in the ribosome. The other two sites are the A-site (aminoacyl), which is the first binding site in the ribosome, and the E-site (exit), the third. During protein translation, the P-site ...
binds a peptidyl-tRNA (a tRNA bound to the poly-peptide chain); and the
E-site The E-site is the third and final binding site for t-RNA in the ribosome during translation, a part of protein synthesis. The "E" stands for exit, and is accompanied by the P-site (for peptidyl) which is the second binding site, and the A-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 (fMet) in bacteria, mitochondria and plastids. The ...
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, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein cha ...
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 covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
of RNA's P-site
adenosine Adenosine ( 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-glycosidic bond. Adenosine is one of the four nucleoside building ...
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-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence ...
. 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 mRNA and the amino ac ...
that matches the current codon (triplet) on the mRNA to append an
amino acid 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 am ...
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 mRNA molecule like “beads” on a “thread”. It consists of a complex of an mRNA molecule and two or more ribosomes that act to translate mRNA instructions into pol ...
''.


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 translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...
. 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, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' 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 cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
, 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 eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...
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 cellular components caused by sources such as reactive oxygen species, free radicals, pe ...
and is, therefore, a
reducing environment A reducing atmosphere is an atmospheric condition in which oxidation is prevented by removal of oxygen and other oxidizing gases or vapours, and which may contain actively reducing gases such as hydrogen, carbon monoxide, and gases such as hydro ...
, proteins containing
disulfide bonds In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
, 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 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classica ...
. 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 bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...
''.


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. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...
s. In eukaryotes, the process takes place both in the cell cytoplasm and in the
nucleolus The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of ...
, 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 eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...
. 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-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence ...
, appearing as a self-replicating complex that only later evolved the ability to synthesize proteins when
amino acid 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 am ...
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 ribosoma ...
could have developed the ability to synthesize
peptide bond In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein cha ...
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 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 mRNA and the amino a ...
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 Gerald Maurice Edelman (; July 1, 1929 – May 17, 2014) was an American biologist who shared the 1972 Nobel Prize in Physiology or Medicine for work with Rodney Robert Porter on the immune system. Edelman's Nobel Prize-winning research concern ...
. 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 cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
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 ''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 ...
, 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 Pseudouridine (abbreviated by the Greek letter psi- Ψ) is an isomer of the nucleoside uridine in which the uracil is attached via a carbon-carbon instead of a nitrogen-carbon glycosidic bond. (In this configuration, uracil is sometimes referred ...
and 2’-O methylation of ribose.


See also

*
Aminoglycoside Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...
s * Biological machines *
Posttranslational modification Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosome ...
*
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 Nucleic acid tertiary structure is the Biomolecular structure#Tertiary structure, three-dimensional shape of a nucleic acid polymer. RNA and DNA molecules are capable of diverse functions ranging from molecular recognition to catalysis. Such fun ...
*
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 of DNA to RNA in the cell's nucleus. The entire process ...
*
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 ...
*
Ada Yonath Ada E. Yonath ( he, עדה יונת, ; born 22 June 1939) is an Israeli crystallographer best known for her pioneering work on the structure of ribosomes. She is the current director of the Helen and Milton A. Kimmelman Center for Biomolecular ...
—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's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
.


References


External links


Lab computer simulates ribosome in motion


Gwen V. Childs, copie


Ribosome
i
''Proteopedia''
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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