EF-Tu
| Elongation Factor Thermo Unstable | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| CDD | cd00881 | ||||||||
| |||||||||
| EF-Tu | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | GTP_EFTU_D2 | ||||||||
| Pfam | PF03144 | ||||||||
| InterPro | IPR004161 | ||||||||
| CDD | cd01342 | ||||||||
| |||||||||
| Elongation factor Tu domain 3 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | GTP_EFTU_D3 | ||||||||
| Pfam | PF03143 | ||||||||
| InterPro | IPR004160 | ||||||||
| CDD | cd01513 | ||||||||
| |||||||||
EF-Tu (elongation factor thermo unstable) is a
As a family of elongation factors, EF-Tu also includes its eukaryotic and archaeal homolog, the alpha subunit of eEF-1 (EF-1A).
Background
Elongation factors are part of the mechanism that synthesizes new
There are three sites on the ribosome for tRNA binding. These are the aminoacyl/acceptor site (abbreviated A), the peptidyl site (abbreviated P), and the exit site (abbreviated E). The P-site holds the tRNA connected to the polypeptide chain being synthesized, and the A-site is the binding site for a charged tRNA with an anticodon complementary to the mRNA codon associated with the site. After binding of a charged tRNA to the A-site, a peptide bond is formed between the growing polypeptide chain on the P-site tRNA and the amino acid of the A-site tRNA, and the entire polypeptide is transferred from the P-site tRNA to the A-site tRNA. Then, in a process catalyzed by the prokaryotic elongation factor EF-G (historically known as translocase), the coordinated translocation of the tRNAs and mRNA occurs, with the P-site tRNA moving to the E-site, where it dissociates from the ribosome, and the A-site tRNA moves to take its place in the P-site.[6][7]
Biological functions
Protein synthesis
EF-Tu participates in the polypeptide elongation process of protein synthesis. In prokaryotes, the primary function of EF-Tu is to transport the correct aa-tRNA to the A-site of the ribosome. As a G-protein, it uses GTP to facilitate its function. Outside of the ribosome, EF-Tu complexed with GTP (EF-Tu • GTP) complexes with aa-tRNA to form a stable EF-Tu • GTP • aa-tRNA ternary complex.[8] EF-Tu • GTP binds all correctly-charged aa-tRNAs with approximately identical affinity, except those charged with initiation residues and selenocysteine.[9][10] This can be accomplished because although different amino acid residues have varying side-chain properties, the tRNAs associated with those residues have varying structures to compensate for differences in side-chain binding affinities.[11][12]
The binding of an aa-tRNA to EF-Tu • GTP allows for the ternary complex to be translocated to the A-site of an active ribosome, in which the anticodon of the tRNA binds to the codon of the mRNA. If the correct anticodon binds to the mRNA codon, the ribosome changes configuration and alters the geometry of the
In the cytoplasm, the deactivated EF-Tu • GDP is acted on by the prokaryotic elongation factor EF-Ts, which causes EF-Tu to release its bound GDP. Upon dissociation of EF-Ts, EF-Tu is able to complex with a GTP due to the 5– to 10–fold higher concentration of GTP than GDP in the cytoplasm, resulting in reactivated EF-Tu • GTP, which can then associate with another aa-tRNA.[8][13]
Maintaining translational accuracy
EF-Tu contributes to translational accuracy in three ways. In translation, a fundamental problem is that near-cognate anticodons have similar binding affinity to a codon as cognate anticodons, such that anticodon-codon binding in the ribosome alone is not sufficient to maintain high translational fidelity. This is addressed by the ribosome not activating the GTPase activity of EF-Tu if the tRNA in the ribosome's A-site does not match the mRNA codon, thus preferentially increasing the likelihood for the incorrect tRNA to leave the ribosome.[14] Additionally, regardless of tRNA matching, EF-Tu also induces a delay after freeing itself from the aa-tRNA, before the aa-tRNA fully enters the A-site (a process called accommodation). This delay period is a second opportunity for incorrectly charged aa-tRNAs to move out of the A-site before the incorrect amino acid is irreversibly added to the polypeptide chain.[15][16] A third mechanism is the less well understood function of EF-Tu to crudely check aa-tRNA associations and reject complexes where the amino acid is not bound to the correct tRNA coding for it.[11]
Other functions
EF-Tu has been found in large quantities in the cytoskeletons of bacteria, co-localizing underneath the cell membrane with MreB, a cytoskeletal element that maintains cell shape.[17][18] Defects in EF-Tu have been shown to result in defects in bacterial morphology.[19] Additionally, EF-Tu has displayed some chaperone-like characteristics, with some experimental evidence suggesting that it promotes the refolding of a number of denatured proteins in vitro.[20][21]
Structure
EF-Tu is a
The GTP-binding domain I undergoes a dramatic conformational change upon GTP hydrolysis to GDP, allowing EF-Tu to dissociate from aa-tRNA and leave the ribosome.[27] Reactivation of EF-Tu is achieved by GTP binding in the cytoplasm, which leads to a significant conformational change that reactivates the tRNA-binding site of EF-Tu. In particular, GTP binding to EF-Tu results in a ~90° rotation of domain I relative to domains II and III, exposing the residues of the tRNA-binding active site.[28]
Domain 2 adopts a
Evolution
 | This section may require cleanup to meet Wikipedia's quality standards. The specific problem is: Still terrible, consider just transcluding the section in "further". (December 2023) |
The GTP-binding domain is
Disease relevance
Along with the ribosome, EF-Tu is one of the most important targets for
See also
- Prokaryotic elongation factors
- EF-Ts (elongation factor thermo stable)
- EF-G (elongation factor G)
- EF-P (elongation factor P)
- eEF-1
- EFR (EF-Tu receptor)
References
- ^ PDB Molecule of the Month EF-Tu
- PMID 1573997.
- ^ "TIGR00485: EF-Tu". National Center for Biotechnology Information. March 3, 2017.
- ^ S2CID 27196901.
- PMID 9332382.
- ^ PMID 15755955.
- ^ S2CID 2078757.
- ^ )
- ^ "Translation elongation factor EFTu/EF1A, bacterial/organelle (IPR004541)". InterPro.
- ^ a b Diwan, Joyce (2008). "Translation: Protein Synthesis". Rensselaer Polytechnic Institute. Archived from the original on 2017-06-30. Retrieved 2017-03-09.
- ^ S2CID 26192336.
- PMID 6370998.
- ^ PMID 9032056.
- PMID 15922593.
- PMID 20427512.
- PMID 27796304.
- PMID 20133608.
- S2CID 40897586.
- S2CID 23701662.
- PMID 9813162.
- PMID 9405422.
- PMID 9758752.
- PMID 8702777.
- PMID 379535.
- S2CID 10644042.
- S2CID 24817616.
- PMID 3126836.
- PMID 8069622.
- S2CID 24817616.
- S2CID 10644042.
- PMID 7556078.
- PMID 7737996.
- S2CID 7417370.
- PMID 1709933.
- S2CID 4251625.
- PMID 1908853.
- PMID 12370016.
- PMID 12932732.
- S2CID 20811259.
External links
- Peptide+Elongation+Factor+Tu at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P49410 (Elongation factor Tu, mitochondrial) at the PDBe-KB.