Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30475211.
- Also identified by DOI 10.7554/eLife.39273 and PMC identifier 6298780.
- Licence recorded as CC0.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
In eukaryotic translation initiation, AUG recognition of the mRNA requires accommodation of Met-tRNA<sub>i</sub> in a 'P<sub>IN</sub>' 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 Å, 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-tRNA<sub>i</sub>. Substitutions of eIF5 residues involved in the eIF5-NTD/tRNA<sub>i</sub> interaction influenced initiation at near-cognate UUG codons<i>in vivo,</i> 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.
Medical subject headings
- Eukaryotic Initiation Factor-1
- Peptide Initiation Factors
- Protein Biosynthesis
- RNA-Binding Proteins
- Ribosomes