Mg2+ and a Key Lysine Modulate Exchange Activity of Eukaryotic Translation Elongation Factor 1Bα

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Journal of Biological Chemistry

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To sustain efficient translation, eukaryotic elongation factor Bα (eEF1Bα) functions as the guanine nucleotide exchange factor for eEF1A. Stopped-flow kinetics using 2′-(or 3′)-O-N-methylanthraniloyl (mant)-GDP showed spontaneous release of nucleotide from eEF1A is extremely slow and accelerated 700-fold by eEF1Bα. The eEF1Bα-stimulated reaction was inhibited by Mg2+ with a K½ of 3.8 mm. Previous structural studies predicted the Lys-205 residue of eEF1Bα plays an important role in promoting nucleotide exchange by disrupting the Mg2+ binding site. Co-crystal structures of the lethal K205A mutant in the catalytic C terminus of eEF1Bα with eEF1A and eEF1A·GDP established that the lethality was not due to a structural defect. Instead, the K205A mutant drastically reduced the nucleotide exchange activity even at very low concentrations of Mg2+.A K205R eEF1Bα mutant on the other hand was functional in vivo and showed nearly wild-type nucleotide dissociation rates but almost no sensitivity to Mg2+. These results indicate the significant role of Mg2+ in the nucleotide exchange reaction by eEF1Bα and establish the catalytic function of Lys-205 in displacing Mg2+ from its binding site.


This article was originally published as Pittman, Y., Valente, L., Jeppesen, M.G., Andersen, G.R., Patel, S. and Kinzy, T.G. (2006) Mg+2 and a key lysine residue modulate guanine nucleotide exchange by eukaryotic translation elongation factor 1Bï¡. J. Biol. Chem. 281:19457-19468. PMID: 16675455