Translation initiation factor 2gamma mutant alters start codon selection independent of Met-tRNA binding.

Selection of the AUG start codon for translation in eukaryotes is governed by codon-anticodon interactions between the initiator Met-tRNA(i)(Met) and the mRNA. Translation initiation factor 2 (eIF2) binds Met-tRNA(i)(Met) to the 40S ribosomal subunit, and previous studies identified Sui(-) mutations in eIF2 that enhanced initiation from a noncanonical UUG codon, ...
presumably by impairing Met-tRNA(i)(Met) binding. Consistently, an eIF2gamma-N135D GTP-binding domain mutation impairs Met-tRNA(i)(Met) binding and causes a Sui(-) phenotype. Intragenic A208V and A382V suppressor mutations restore Met-tRNA(i)(Met) binding affinity and cell growth; however, only A208V suppresses the Sui(-) phenotype associated with the eIF2gamma-N135D mutation. An eIF2gamma-A219T mutation impairs Met-tRNA(i)(Met) binding but unexpectedly enhances the fidelity of initiation, suppressing the Sui(-) phenotype associated with the eIF2gamma-N135D,A382V mutant. Overexpression of eIF1, which is thought to monitor codon-anticodon interactions during translation initiation, likewise suppresses the Sui(-) phenotype of the eIF2gamma mutants. We propose that structural alterations in eIF2gamma subtly alter the conformation of Met-tRNA(i)(Met) on the 40S subunit and thereby affect the fidelity of start codon recognition independent of Met-tRNA(i)(Met) binding affinity.
Mesh Terms:
Amino Acid Sequence, Basic-Leucine Zipper Transcription Factors, Codon, Initiator, DNA-Binding Proteins, Eukaryotic Initiation Factor-2, Models, Molecular, Molecular Sequence Data, Mutation, Nucleic Acid Conformation, Phenotype, Protein Structure, Tertiary, RNA, Transfer, Met, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Alignment, Transcription Factors
Mol. Cell. Biol.
Date: Nov. 01, 2008
Download Curated Data For This Publication
116025
Switch View:
  • Interactions 3