Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome. EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution. Elongation factor EF1B (also known as EF-Ts or EF-1beta/gamma/delta) is a nucleotide exchange factor that is required to regenerate EF1A from its inactive form (EF1A-GDP) to its active form (EF1A-GTP). EF1A is then ready to interact with a new aminoacyl-tRNA to begin the cycle again. EF1B is more complex in eukaryotes than in bacteria, and can consist of three subunits: EF1B-alpha (or EF-1beta), EF1B-gamma (or EF-1gamma) and EF1B-beta (or EF-1delta). This entry represents the guanine nucleotide exchange domain of the beta (EF-1beta, also known as EF1B-alpha) and delta (EF-1delta, also known as EF1B-beta) chains of EF1B proteins from eukaryotes and archaea. The beta and delta chains have exchange activity, which mainly resides in their homologous guanine nucleotide exchange domains, found in the C-terminal region of the peptides. Their N-terminal regions may be involved in interactions with the gamma chain (EF-1gamma).
Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome [ (PUBMED:12762045) (PUBMED:15922593) (PUBMED:12932732) ]. EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.
Elongation factor EF1B (also known as EF-Ts or EF-1beta/gamma/delta) is a nucleotide exchange factor that is required to regenerate EF1A from its inactive form (EF1A-GDP) to its active form (EF1A-GTP). EF1A is then ready to interact with a new aminoacyl-tRNA to begin the cycle again. EF1B is more complex in eukaryotes than in bacteria, and can consist of three subunits: EF1B-alpha (or EF-1beta), EF1B-gamma (or EF-1gamma) and EF1B-beta (or EF-1delta) [ (PUBMED:12762045) ].
This entry represents the guanine nucleotide exchange domain of the beta (EF-1beta, also known as EF1B-alpha) and delta (EF-1delta, also known as EF1B-beta) chains of EF1B proteins from eukaryotes and archaea. The beta and delta chains have exchange activity, which mainly resides in their homologous guanine nucleotide exchange domains, found in the C-terminal region of the peptides. Their N-terminal regions may be involved in interactions with the gamma chain (EF-1gamma).
The ribosome is a complex macromolecular assembly capable of translatingmRNA sequence into amino acid sequence. The adaptor molecule oftranslation is tRNA, but the delivery of aminoacyl-tRNAs--the primarysubstrate of the ribosome--relies on the formation of a ternary complexwith elongation factor Tu (EF-Tu) and GTP. Likewise, elongation factor G(EF-G) is required to reset the elongation cycle through the translocationof tRNAs. Recent structures and biochemical data on ribosomes in complexwith the ternary complex or EF-G have shed light on the mode of action ofthe elongation factors, and how this interplays with the state of tRNAsand the ribosome. A model emerges of the specific routes of conformationalchanges mediated by tRNA and the ribosome that trigger the GTPase activityof the elongation factors on the ribosome.
Translation elongation factors are the workhorses of protein synthesis onthe ribosome. They assist in elongating the nascent polypeptide chain byone amino acid at a time. The general biochemical outline of thetranslation elongation cycle is well preserved in all biological kingdoms.Recently, there has been structural insight into the effects ofantibiotics on elongation. These structures provide a scaffold forunderstanding the biological function of elongation factors beforehigh-resolution structures of such factors in complex with ribosomes areobtained. Very recent structures of the yeast translocation factor and itscomplex with the antifungal drug sordarin reveal an unexpectedconformational flexibility that might be crucial to the mechanism oftranslocation.
The solution structure of the guanine nucleotide exchange domain of humanelongation factor 1beta reveals a striking resemblance to that of EF-Tsfrom Escherichia coli.
Structure. 1999; 7: 217-26
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BACKGROUND: In eukaryotic protein synthesis, the multi-subunit elongationfactor 1 (EF-1) plays an important role in ensuring the fidelity andregulating the rate of translation. EF-1alpha, which transports theaminoacyl tRNA to the ribosome, is a member of the G-protein superfamily.EF-1beta regulates the activity of EF-1alpha by catalyzing the exchange ofGDP for GTP and thereby regenerating the active form of EF-1alpha. Thestructure of the bacterial analog of EF-1alpha, EF-Tu has been solved incomplex with its GDP exchange factor, EF-Ts. These structures indicate amechanism for GDP-GTP exchange in prokaryotes. Although there is goodsequence conservation between EF-1alpha and EF-Tu, there is essentially nosequence similarity between EF-1beta and EF-Ts. We wished to explorewhether the prokaryotic exchange mechanism could shed any light on themechanism of eukaryotic translation elongation. RESULTS: Here, we reportthe structure of the guanine-nucleotide exchange factor (GEF) domain ofhuman EF-1beta (hEF-1beta, residues 135-224); hEF-1beta[135-224],determined by nuclear magnetic resonance spectroscopy. Sequenceconservation analysis of the GEF domains of EF-1 subunits beta and deltafrom widely divergent organisms indicates that the most highly conservedresidues are in two loop regions. Intriguingly, hEF-1beta[135-224] sharesstructural homology with the GEF domain of EF-Ts despite their differentprimary sequences. CONCLUSIONS: On the basis of both the structuralhomology between EF-Ts and hEF-1beta[135-224] and the sequenceconservation analysis, we propose that the mechanism of guanine-nucleotideexchange in protein synthesis has been conserved in prokaryotes andeukaryotes. In particular, Tyr181 of hEF-1beta[135-224] appears to beanalogous to Phe81 of Escherichia coli EF-Ts.
