Elongation factors are a set of proteins that function at the ribosome, during protein synthesis, to facilitate translational elongation from the formation of the first to the last peptide bond of a growing polypeptide. Most common elongation factors in prokaryotes are EF-Tu, EF-Ts, EF-G.[1] Bacteria and eukaryotes use elongation factors that are largely homologous to each other, but with distinct structures and different research nomenclatures.[2]
Elongation is the most rapid step in translation.[3] In bacteria, it proceeds at a rate of 15 to 20 amino acids added per second (about 45-60 nucleotides per second).[citation needed] In eukaryotes the rate is about two amino acids per second (about 6 nucleotides read per second).[citation needed] Elongation factors play a role in orchestrating the events of this process, and in ensuring the high accuracy translation at these speeds.[citation needed]
YouTube Encyclopedic
-
1/5Views:143 59528 14232 07111 0683 942
-
Eukaryotic Translation (Protein Synthesis), Animation.
-
Translation (Part 6 of 8) - Elongation
-
Translation elongation | translation in prokaryotes lecture 4
-
Detailed Description of Protein Translation
-
Eukaryotic Translation Initation
Transcription
Steps of the translation process: Initiation : The small ribosomal subunit binds to the initiator tRNA carrying the initiator amino acid methionine. This complex then attaches to the cap structure at the 5’ end of an mRNA and scans for the start codon AUG. The process is mediated by several initiation factors. At the start codon, the large ribosomal subunit joins the complex and all initiation factors are released. The ribosome has three sites: the A-site is the entry site for new tRNA charged with amino-acid or aminoacyl-tRNA; the P-site is occupied by peptidyl-tRNA - the tRNA that carries the growing polypeptide chain; the E-site is the exit site for the tRNA after it’s done delivering the amino acid. The initiator tRNA is positioned in the P-site. Elongation: A new tRNA carrying an amino acid enters the A-site of the ribosome. On the ribosome, the anticodon of the incoming tRNA is matched against the mRNA codon positioned in the A-site. During this proof-reading, tRNA with incorrect anticodons are rejected and replaced by new tRNA that are again checked. When the right aminoacyl-tRNA enters the A-site, a peptide bond is made between the two now-adjacent amino-acids. As the peptide bond is formed, the tRNA in the P-site releases the amino-acids onto the tRNA in the A-site and becomes empty. At the same time, the ribosome moves one triplet forward on the mRNA. As a result, the empty tRNA is now in the E-site and the peptidyl tRNA is in the P-site. The A-site is now unoccupied and is ready to accept a new tRNA. The cycle is repeated for each codon on the mRNA. Termination: Termination happens when one of the three stop codons is positioned in the A-site. No tRNA can fit in the A-site at that point as there are no tRNA that match the sequence. Instead, these codons are recognized by a protein, a release factor. Binding of the release factor catalyzes the cleavage of the bond between the polypeptide and the tRNA. The polypeptide is released from the ribosome. The ribosome is disassociated into subunits and is ready for a new round of translation.
Nomenclature of homologous EFs
| Bacterial | Eukaryotic/Archaeal | Function |
|---|---|---|
| EF-Tu | eEF-1A (α)[2] | mediates the entry of the aminoacyl tRNA into a free site of the ribosome.[4] |
| EF-Ts | eEF-1B (βγ)[2] | serves as the guanine nucleotide exchange factor for EF-Tu, catalyzing the release of GDP from EF-Tu.[2] |
| EF-G | eEF-2 | catalyzes the translocation of the tRNA and mRNA down the ribosome at the end of each round of polypeptide elongation. Causes large conformation changes.[5] |
| EF-P | eIF-5A | possibly stimulates formation of peptide bonds and resolves stalls.[6] |
| EF-4 | (None) | Proofreading |
| Note that EIF5A, the archaeal and eukaryotic homolog to EF-P, was named as an initiation factor but now considered an elongation factor as well.[6] | ||
In addition to their cytoplasmic machinery, eukaryotic mitochondria and plastids have their own translation machinery, each with their own set of bacterial-type elongation factors.[7][8] In humans, they include TUFM, TSFM, GFM1, GFM2, GUF1; the nominal release factor MTRFR may also play a role in elongation.[9]
In bacteria, selenocysteinyl-tRNA requires a special elongation factor SelB (P14081) related to EF-Tu. A few homologs are also found in archaea, but the functions are unknown.[10]
As a target
Elongation factors are targets for the toxins of some pathogens. For instance, Corynebacterium diphtheriae produces diphtheria toxin, which alters protein function in the host by inactivating elongation factor (EF-2). This results in the pathology and symptoms associated with diphtheria. Likewise, Pseudomonas aeruginosa exotoxin A inactivates EF-2.[11]
References
- ^ Parker, J. (2001). "Elongation Factors; Translation". Encyclopedia of Genetics. pp. 610–611. doi:10.1006/rwgn.2001.0402. ISBN 9780122270802.
- ^ a b c d Sasikumar, Arjun N.; Perez, Winder B.; Kinzy, Terri Goss (July 2012). "The Many Roles of the Eukaryotic Elongation Factor 1 Complex". Wiley Interdisciplinary Reviews. RNA. 3 (4): 543–555. doi:10.1002/wrna.1118. ISSN 1757-7004. PMC 3374885. PMID 22555874.
- ^ Prabhakar, Arjun; Choi, Junhong; Wang, Jinfan; Petrov, Alexey; Puglisi, Joseph D. (July 2017). "Dynamic basis of fidelity and speed in translation: Coordinated multistep mechanisms of elongation and termination". Protein Science. 26 (7): 1352–1362. doi:10.1002/pro.3190. ISSN 0961-8368. PMC 5477533. PMID 28480640.
- ^ Weijland A, Harmark K, Cool RH, Anborgh PH, Parmeggiani A (March 1992). "Elongation factor Tu: a molecular switch in protein biosynthesis". Molecular Microbiology. 6 (6): 683–8. doi:10.1111/j.1365-2958.1992.tb01516.x. PMID 1573997.
- ^ Jørgensen, R; Ortiz, PA; Carr-Schmid, A; Nissen, P; Kinzy, TG; Andersen, GR (May 2003). "Two crystal structures demonstrate large conformational changes in the eukaryotic ribosomal translocase". Nature Structural Biology. 10 (5): 379–85. doi:10.1038/nsb923. PMID 12692531. S2CID 4795260.
- ^ a b Rossi, D; Kuroshu, R; Zanelli, CF; Valentini, SR (2013). "eIF5A and EF-P: two unique translation factors are now traveling the same road". Wiley Interdisciplinary Reviews. RNA. 5 (2): 209–22. doi:10.1002/wrna.1211. PMID 24402910. S2CID 25447826.
- ^ Manuell, Andrea L; Quispe, Joel; Mayfield, Stephen P; Petsko, Gregory A (7 August 2007). "Structure of the Chloroplast Ribosome: Novel Domains for Translation Regulation". PLOS Biology. 5 (8): e209. doi:10.1371/journal.pbio.0050209. PMC 1939882. PMID 17683199.
- ^ G C Atkinson; S L Baldauf (2011). "Evolution of elongation factor G and the origins of mitochondrial and chloroplast forms". Molecular Biology and Evolution. 28 (3): 1281–92. doi:10.1093/molbev/msq316. PMID 21097998.
- ^ "KEGG DISEASE: Combined oxidative phosphorylation deficiency". www.genome.jp.
- ^ Atkinson, Gemma C; Hauryliuk, Vasili; Tenson, Tanel (21 January 2011). "An ancient family of SelB elongation factor-like proteins with a broad but disjunct distribution across archaea". BMC Evolutionary Biology. 11 (1): 22. doi:10.1186/1471-2148-11-22. PMC 3037878. PMID 21255425.
- ^ Lee H, Iglewski WJ (1984). "Cellular ADP-ribosyltransferase with the same mechanism of action as diphtheria toxin and Pseudomonas toxin A". Proc. Natl. Acad. Sci. U.S.A. 81 (9): 2703–7. Bibcode:1984PNAS...81.2703L. doi:10.1073/pnas.81.9.2703. PMC 345138. PMID 6326138.
Further reading
- Alberts, B. et al. (2002). Molecular Biology of the Cell, 4th ed. New York: Garland Science. ISBN 0-8153-3218-1.[page needed]
- Berg, J. M. et al. (2002). Biochemistry, 5th ed. New York: W.H. Freeman and Company. ISBN 0-7167-3051-0.[page needed]
- Singh, B. D. (2002). Fundamentals of Genetics, New Delhi, India: Kalyani Publishers. ISBN 81-7663-109-4.[page needed]
External links
- nobelprize.org Explaining the function of eukaryotic elongation factors
- Elongation+Factor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Peptide+Elongation+Factor+G at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Peptide+Elongation+Factor+Tu at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- EC 3.6.5.3
This page was last edited on 14 November 2023, at 00:01