Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition.
Elife
; 72018 11 30.
Article
in En
| MEDLINE
| ID: mdl-30475211
ABSTRACT
In eukaryotic translation initiation, AUG recognition of the mRNA requires accommodation of Met-tRNAi 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 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-tRNAi. Substitutions of eIF5 residues involved in the eIF5-NTD/tRNAi interaction influenced initiation at near-cognate UUG codonsin vivo, and the closed/open PIC conformation in vitro, consistent with direct stabilization of the codonanticodon duplex by the wild-type eIF5-NTD. The present structure reveals the basis for a key role of eIF5 in start-codon selection.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ribosomes
/
Protein Biosynthesis
/
Eukaryotic Initiation Factor-1
/
Peptide Initiation Factors
/
RNA-Binding Proteins
Language:
En
Journal:
Elife
Year:
2018
Document type:
Article
Affiliation country:
Reino Unido