The solution structure of the guanine nucleotide exchange domain of human elongation factor 1β reveals a striking resemblance to that of EF-Ts from Escherichia coli

Background: In eukaryotic protein synthesis, the multi-subunit elongation factor 1 (EF-1) plays an important role in ensuring the fidelity and regulating the rate of translation. EF-1 alpha, which transports the aminoacyl tRNA to the ribosome, is a member of the G-protein superfamily. EF-1 beta regulates the activity of EF-1 alpha by catalyzing the exchange of GDP for GTP and thereby regenerating the active form of EF-1 alpha. The structure of the bacterial analog of EF-1 alpha, EF-TU has been solved in complex with its GDP exchange factor, EF-Ts. These structures indicate a mechanism for GDP-GTP exchange in prokatyotes. Although there is good sequence conservation between EF-1 alpha and EF-Tu, there is essentially no sequence similarity between EF-1 beta and EF-Ts. We wished to explore whether the prokaryotic exchange mechanism could shed any light on the mechanism of eukaryotic translation elongation. Results: Here, we report the structure of the guanine-nucleotide exchange factor (GEF) domain of human EF-1 beta (hEF-1 beta, residues 135-224); hEF-1 beta[135-224], determined by nuclear magnetic resonance spectroscopy. Sequence conservation analysis of the GEF domains of EF-1 subunits beta and delta from widely divergent organisms indicates that the most highly conserved residues ate in two loop regions. Intriguingly, hEF-1 beta[135-224] shares structural homology with the GEF domain of EF-Ts despite their different primary sequences. Conclusions: On the basis of both the structural homology between EF-Ts and hEF-1 beta[135-224] and the sequence conservation analysis, we propose that the mechanism of guanine-nucleotide exchange in protein synthesis has been conserved in prokaryotes and eukaryotes. In particular, Tyr181 of hEF-1 beta[135-224] appears to be analogous to Phe81 of Escherichia coli EF-Ts.