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Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition

Luis Llacer, Jose and Hussain, Tanweer and Saini, Adesh K and Nanda, Jagpreet Singh and Kaur, Sukhvir and Gordiyenko, Yuliya and Kumar, Rakesh and Hinnebusch, Alan G and Lorsch, Jon R and Ramakrishnan, Venki (2018) Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition. In: ELIFE, 7 .

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Official URL: https://doi.org/10.7554/eLife.39273

Abstract

In eukaryotic translation initiation, AUG recognition of the mRNA requires accommodation of Met-tRNA(i) in a `PIN' state, which is antagonized by the factor eIF1. eIF5 is a GTPase activating protein (GAP) of eIF2 that additionally promotes stringent AUG selection, but the molecular basis of its dual function was unknown. We present a cryo-electron microscopy (cryo-EM) reconstruction of a yeast 48S pre-initiation complex (PIC), at an overall resolution of 3.0 angstrom, featuring the N-terminal domain (NTD) of eIF5 bound to the 40S subunit at the location vacated by eIF1. eIF5 interacts with and allows a more accommodated orientation of Met-tRNAi. Substitutions of eIF5 residues involved in the eIF5-NTD/tRNAi interaction influenced initiation at near-cognate UUG codons in vivo, and the closed/open PIC conformation in vitro, consistent with direct stabilization of the codon:anticodon duplex by the wild-type eIF5-NTD. The present structure reveals the basis for a key role of eIF5 in start-codon selection.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to ELIFE SCIENCES PUBLICATIONS LTD
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Depositing User: Id for Latest eprints
Date Deposited: 28 Jan 2019 08:39
Last Modified: 28 Jan 2019 08:39
URI: http://eprints.iisc.ac.in/id/eprint/61457

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