Crystal structures of nucleotide exchange intermediates in the eEF1A-eEF1Bα complex

In the elongation cycle of protein biosynthesis, the nucleotide exchange factor eEF1B alpha catalyzes the exchange of GDP bound to the G-protein, eEF1A, for GTP. To obtain more information about the recently solved eEF1A-eF1B alpha structure, we determined the structures of the eEF1A-eEF1B alpha -GDP-Mg2+, eEIF1A-eEF1B alpha -GDP and eEF1A-eEF1B alpha -GDPNP complexes at 3.0, 2.4 and 2.05 Angstrom resolution, respectively. Minor changes, specifically around the nucleotide binding site, in eEF1A and eEF1Ba are consistent with in vivo data. The base, sugar and alpha -phosphate bind as in other known nucleotide G-protein complexes, whereas the beta- and gamma -phosphates are disordered. A mutation of Lys 205 in eEF1B alpha that inserts into the Mg2+ binding site of eEF1A is lethal. This together with the structures emphasizes the essential role of Mg2+ in nucleotide exchange in the eEF1A-eEF1B alpha complex.