eIF2? zinc-binding domain interacts with the eIF2? subunit through the guanine nucleotide binding interface to promote Met-tRNAiMet binding.

The heterotrimeric eIF2 complex consists of a core eIF2? subunit to which binds eIF2? and eIF2? subunits and plays an important role in delivering the Met-tRNAiMet to the 40S ribosome and start codon selection. The intricacies of eIF2?-? interaction in promoting Met-tRNAiMet binding are not clearly understood. Previously, the zinc-binding ...
domain (ZBD) eIF2?S264Y mutation was reported to cause Met-tRNAiMet binding defect due to the intrinsic GTPase activity. We showed that the eIF2?S264Y mutation has eIF2?-? interaction defect. Consistently, the eIF2?T238A intragenic suppressor mutation restored the eIF2?-? and Met-tRNAiMet binding. The eIF2?-ZBD residues Asn252Asp and Arg253Ala mutation caused Met-tRNAiMet binding defect that was partially rescued by the eIF2?T238A mutation, suggesting the eIF2?-ZBD modulates Met-tRNAiMet binding. The suppressor mutation rescued the translation initiation fidelity defect of the eIF2?N135D SW-I mutation and eIF2?F217A/Q221A double mutation in the HTH domain. The eIF2?T238A suppressor mutation could not rescue the eIF2? binding defect of the eIF2?V281K mutation; however, combining the eIF2?S264Y mutation with the eIF2?V281K mutation was lethal. In addition to the previously known interaction of eIF2? with the eIF2? subunit via its ?1-helix, the eIF2?-ZBD also interacts with the eIF2? subunit via guanine nucleotide-binding interface; thus, the eIF2?-? interacts via two distinct binding sites.
Mesh Terms:
Binding Sites, Eukaryotic Initiation Factor-2, Eukaryotic Initiation Factor-2B, Humans, Mutation, Protein Binding, RNA, Transfer, Met, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Zinc
Biosci Rep
Date: Jul. 31, 2024
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