Eukaryotic translation elongation (Homo sapiens)
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Description
The translation elongation cycle adds one amino acid at a time to a growing polypeptide according to the sequence of codons found in the mRNA. The next available codon on the mRNA is exposed in the aminoacyl-tRNA (aa-tRNA) binding site (A site) on the 30S subunit.
A: Ternary complexes of aa -tRNA:eEF1A:GTP enter the ribosome and enable the anticodon of the tRNA to make a codon/anticodon interaction with the A-site codon of the mRNA. B: Upon cognate recognition, the eEF1A:GTP is brought into the GTPase activating center of the ribosome, GTP is hydrolyzed and eEF1A:GDP leaves the ribosome. C: The peptidyl transferase center of ribosome catalyses the formation of a peptide bond between the incoming amino acid and the peptide found in the peptidyl-tRNA binding site (P site). D: In the pre-translocation state of the ribosome, the eEF2:GTP enters the ribosome, physically translocating the peptidyl-tRNA out of the A site to P site and leaves the ribosome eEF2:GDP. This action of eEF2:GTP accounts for the precise movement of the mRNA by 3 nucleotides.Consequently, deacylated tRNA is shifted to the E site. A ribosome associated ATPase activity is proposed to stimulate the release of deacylated tRNA from the E site subsequent to translocation (Elskaya et al., 1991). In this post-translocation state, the ribosome is now ready to receive a new ternary complex.
This process is illustrated below with: an amino acyl-tRNA with an amino acid, a peptidyl-tRNA with a growing peptide, a deacylated tRNA with an -OH, and a ribosome with A,P and E sites to accommodate these three forms of tRNA. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=156842
A: Ternary complexes of aa -tRNA:eEF1A:GTP enter the ribosome and enable the anticodon of the tRNA to make a codon/anticodon interaction with the A-site codon of the mRNA. B: Upon cognate recognition, the eEF1A:GTP is brought into the GTPase activating center of the ribosome, GTP is hydrolyzed and eEF1A:GDP leaves the ribosome. C: The peptidyl transferase center of ribosome catalyses the formation of a peptide bond between the incoming amino acid and the peptide found in the peptidyl-tRNA binding site (P site). D: In the pre-translocation state of the ribosome, the eEF2:GTP enters the ribosome, physically translocating the peptidyl-tRNA out of the A site to P site and leaves the ribosome eEF2:GDP. This action of eEF2:GTP accounts for the precise movement of the mRNA by 3 nucleotides.Consequently, deacylated tRNA is shifted to the E site. A ribosome associated ATPase activity is proposed to stimulate the release of deacylated tRNA from the E site subsequent to translocation (Elskaya et al., 1991). In this post-translocation state, the ribosome is now ready to receive a new ternary complex.
This process is illustrated below with: an amino acyl-tRNA with an amino acid, a peptidyl-tRNA with a growing peptide, a deacylated tRNA with an -OH, and a ribosome with A,P and E sites to accommodate these three forms of tRNA. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=156842
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- Carvalho MD, Carvalho JF, Merrick WC.; ''Biological characterization of various forms of elongation factor 1 from rabbit reticulocytes.''; PubMed Europe PMC Scholia
- Pérez JM, Siegal G, Kriek J, Hård K, Dijk J, Canters GW, Möller W.; ''The solution structure of the guanine nucleotide exchange domain of human elongation factor 1beta reveals a striking resemblance to that of EF-Ts from Escherichia coli.''; PubMed Europe PMC Scholia
- Van Ness BG, Howard JB, Bodley JW.; ''ADP-ribosylation of elongation factor 2 by diphtheria toxin. Isolation and properties of the novel ribosyl-amino acid and its hydrolysis products.''; PubMed Europe PMC Scholia
- Veremieva M, Khoruzhenko A, Zaicev S, Negrutskii B, El'skaya A.; ''Unbalanced expression of the translation complex eEF1 subunits in human cardioesophageal carcinoma.''; PubMed Europe PMC Scholia
- Guillot D, Penin F, Di Pietro A, Sontag B, Lavergne JP, Reboud JP.; ''GTP binding to elongation factor eEF-2 unmasks a tryptophan residue required for biological activity.''; PubMed Europe PMC Scholia
- Van Ness BG, Howard JB, Bodley JW.; ''ADP-ribosylation of elongation factor 2 by diphtheria toxin. NMR spectra and proposed structures of ribosyl-diphthamide and its hydrolysis products.''; PubMed Europe PMC Scholia
- Kapp LD, Lorsch JR.; ''The molecular mechanics of eukaryotic translation.''; PubMed Europe PMC Scholia
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Annotated Interactions
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| Source | Target | Type | Database reference | Comment |
|---|---|---|---|---|
| 80S
Met-tRNAi mRNA aminoacyl-tRNA | Arrow | REACT_552 (Reactome)  | ||
| 80S
Met-tRNAi mRNA | REACT_2075 (Reactome) | |||
| 80S Ribosome
mRNA peptidyl-tRNA with elongating peptide | Arrow | REACT_1937 (Reactome) | ||
| 80S ribosome | mim-catalysis | REACT_1227 (Reactome) | ||
| 80S ribosome | mim-catalysis | REACT_552 (Reactome) | ||
| Aminoacyl-tRNA | REACT_1242 (Reactome) | |||
| EEF1A1 | REACT_90 (Reactome) | |||
| EEF1A1 | mim-catalysis | REACT_90 (Reactome) | ||
| EEF1B2 | REACT_1395 (Reactome) | |||
| EEF1D | REACT_1395 (Reactome) | |||
| EEF1G | REACT_1395 (Reactome) | |||
| EEF2 | REACT_2173 (Reactome) | |||
| Elongation complex with growing peptide chain | REACT_1937 (Reactome) | |||
| GTP | REACT_2173 (Reactome) | |||
| GTP | REACT_67 (Reactome) | |||
| GTP | REACT_90 (Reactome) | |||
| Pi | Arrow | REACT_1937 (Reactome) | ||
| Pi | Arrow | REACT_552 (Reactome) | ||
| REACT_1227 (Reactome) | The A- and P-sites of the ribosome positions the aa-tRNA and peptidyl-tRNA such that a nucleophilic attack can occur between the amine group of the A-site aa-tRNA and the carbonyl group of the growing peptide chain on the P-site tRNA, resulting in the formation of a peptide bond. The carboxyl end of the peptide chain is uncoupled from the tRNA molecule in the P-site and forms a new peptide bond with the amino acid that is in the A-site. This process is illustrated below with: a peptidyl-tRNA with a growing peptide,a deacylated tRNA with an -OH and a ribosome with A,P and E sites to accommodate these three forms of tRNA. | |||
| REACT_1242 (Reactome) | The binding of eEF1A:GTP to aminoacyl tRNA (aa-tRNA) results in the formation of a ternary complex (eEF1A:GTP:aa-tRNA). Human eEF1A and rabbit eEF1A are 100% identical, and prokaryotic homologue of eEF1A (EF-Tu) shows 59% identity in the GTP-binding domain.This process is illustrated below with: a GTP molecule in white and eEF1A protein in yellow. | |||
| REACT_1395 (Reactome) | At the beginning of this reaction, 1 molecule of 'eEF1B alpha', 1 molecule of 'eEF1B gamma', and 1 molecule of 'eEF1B beta' are present. At the end of this reaction, 1 molecule of 'eEF1B complex' is present. This reaction takes place in the 'cytosol'. | |||
| REACT_1937 (Reactome) | Following peptide bond formation, GTP-bound eEF2 catalyzes the translocation of the deacylated tRNA in the P-site and the peptidyl-tRNA in the A-site (the pre-translocation state) into the E- and P- sites (the post-translocation state), respectively. Thus, the mRNA advances by three bases to expose the next codon in the A-site. After translocation, GDP-bound eEF2 leaves the ribosome to allow another round of elongation. eEF2 is reactivated by the release of GDP and binds GTP for subsequent rounds. This process is illustrated below with a peptidyl-tRNA with a growing peptide, a deacylated tRNA with an -OH and a ribosome with A,P and E sites to accommodate these three forms of tRNA is also shown. | |||
| REACT_2075 (Reactome) | Once the correct codon-anticodon match occurs between the mRNA and aa-tRNA, the decoding event triggers GTP hydrolysis on eEF1A. The resulting conformational change releases the aa-tRNA to the A-site, and GDP bound form eEF1A is released from the ribosome. Insight into the mechanics of this system has been obtained from earlier works with rabbit reticulocytes and the E.coli system. This process is illustrated below with: an amino acyl-tRNA with an amino acid, a peptidyl-tRNA with a growing peptide and a ribosome with A,P and E sites to accommodate these two forms of tRNA. | |||
| REACT_2173 (Reactome) | At the beginning of this reaction, 1 molecule of 'eEF2', and 1 molecule of 'GTP' are present. At the end of this reaction, 1 molecule of 'eEF2:GTP' is present. This reaction takes place in the 'cytosol'. | |||
| REACT_552 (Reactome) | Once the correct codon-anticodon match occurs between the mRNA and aa-tRNA, the decoding event triggers GTP hydrolysis on eEF1A. The resulting conformational change releases the aa-tRNA to the A-site, and GDP bound form of eEF1A is released from the ribosome. This process is illustrated below with: an amino acyl-tRNA with an amino acid,a peptidyl-tRNA with a growing peptide and a ribosome with A,P and E sites to accommodate these two forms of tRNA. | |||
| REACT_67 (Reactome) | The eEF1B complex binds to eEF1A and regulates its activity by catalyzing the release of GDP. Subsequently, GTP is able to bind eEF1A allowing the formation of the ternary complex (eEF1A-GTP-aa-tRNA).In metazoans eEF1 protein family is composed of four subunits: eEF1A and eEF1B alpha, beta, and gamma (formerly EF-1alpha, EF-1beta, EF-1delta, and EF-1gamma, respectively). Both eEF1B alpha and eEF1B beta function as nucleotide exchange proteins. eEF1B gamma associates with eEF1B alpha and stimulates its exchange activity. This process is illustrated below with a GTP molecule in white and eEF1A protein in yellow.The three subunits of eEF1B are also shown. | |||
| REACT_90 (Reactome) | The cycle of elongation starts with an empty ribosomal A-site and the peptidyl-tRNA in the P-site. eEF1A is activated by GTP binding and allows for the subsequent binding of aminoacyl-tRNA (aa-tRNA).This process is illustrated below with a GTP molecule in white and eEF1A protein in yellow. | |||
| eEF1A GDP | Arrow | REACT_1937 (Reactome) | ||
| eEF1A GDP | Arrow | REACT_552 (Reactome) | ||
| eEF1A GDP | REACT_67 (Reactome) | |||
| eEF1A
GTP aminoacyl-tRNA complex | REACT_1937 (Reactome) | |||
| eEF1A
GTP aminoacyl-tRNA complex | REACT_2075 (Reactome) | |||
| eEF1A GTP | Arrow | REACT_67 (Reactome) | ||
| eEF1A GTP | REACT_1242 (Reactome) | |||
| eEF1B GDP exchange complex | Arrow | REACT_67 (Reactome) | ||
| eEF1B complex | REACT_67 (Reactome) | |||
| eEF1B complex | mim-catalysis | REACT_67 (Reactome) | ||
| eEF2 GDP | Arrow | REACT_1937 (Reactome) | ||
| eEF2 GTP | REACT_1937 (Reactome) |
