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

• Published in: Structure (London) 1999, Vol.7 (2), p.217-226
• Main Authors: Pérez, Janice MJ, Siegal, Gregg, Kriek, Jan, Hård, Karl, Dijk, Jan, Canters, Gerard W, Möller, Wim
• Format: Article
• Language: English
• Subjects: G protein; guanine-nucleotide exchange factor; NMR; translation elongation
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/S0969-2126(99)80027-6

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-1α, which transports the aminoacyl tRNA to the ribosome, is a member of the G-protein superfamily. EF-1β regulates the activity of EF-1α by catalyzing the exchange of GDP for GTP and thereby regenerating the active form of EF-1α. The structure of the bacterial analog of EF-1α, EF-Tu has been solved in complex with its GDP exchange factor, EF-Ts. These structures indicate a mechanism for GDP–GTP exchange in prokaryotes. Although there is good sequence conservation between EF-1α and EF-Tu, there is essentially no sequence similarity between EF-1β 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-1β (hEF-1β, residues 135–224); hEF-1β[135–224], determined by nuclear magnetic resonance spectroscopy. Sequence conservation analysis of the GEF domains of EF-1 subunits β and δ from widely divergent organisms indicates that the most highly conserved residues are in two loop regions. Intriguingly, hEF-1β[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-1β[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-1β[135–224] appears to be analogous to Phe81 of Escherichia coli EF-Ts.