Mutations in Elongation Factor 1β, a Guanine Nucleotide Exchange Factor, Enhance Translational Fidelity

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Molecular and Cellular Biology

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Translation elongation factor 1β (EF-1β) is a member of the family of guanine nucleotide exchange factors, proteins whose activities are important for the regulation of G proteins critical to many cellular processes. EF-1β is a highly conserved protein that catalyzes the exchange of bound GDP for GTP on EF-1α, a required step to ensure continued protein synthesis. In this work, we demonstrate that the highly conserved C-terminal region of Saccharomyces cerevisiae EF-1β is sufficient for normal cell growth. This region of yeast and metazoan EF-1β and the metazoan EF-1β-like protein EF-1δ is highly conserved. Human EF-1β, but not human EF-1δ, is functional in place of yeast EF-1β, even though both EF-1β and EF-1δ have previously been shown to have guanine nucleotide exchange activity in vitro. Based on the sequence and functional homology, mutagenesis of two C-terminal residues identical in all EF-1β protein sequences was performed, resulting in mutants with growth defects and sensitivity to translation inhibitors. These mutants also enhance translational fidelity at nonsense codons, which correlates with a reduction in total protein synthesis. These results indicate the critical function of EF-1β in regulating EF-1α activity, cell growth, translation rates, and translational fidelity.


This article was originally published as Carr-Schmid, A., Valente, L., Loik, V.I., Williams, T., Starita, L.M. and Kinzy, T.G. (1999) Mutations in Elongation Factor 1ï¢, a Guanine Nucleotide Exchange Factor, Enhance Translational Fidelity, Mol. Cell. Biol. 19, 5257-5266. PMID: 10409717