8RW1

Structure of a yeast 48S-AUC preinitiation complex in closed conformation

Summary for 8RW1

• Entry DOI: 10.2210/pdb8rw1/pdb
• EMDB information: 19541
• Descriptor: 18S ribosomal RNA, KLLA0A10483p, KLLA0F18040p, ... (46 entities in total)
• Functional Keywords: ribosome, translation, initiation factors, 40s, eif1a, auc codon, eif2, trnai, 48s pic, small ribosome subunit
• Biological source: Saccharomyces cerevisiae S288C; More
• Total number of polymer chains: 41
• Total formula weight: 1362122.81

Authors

Villamayor-Belinchon, L.,Sharma, P.,Llacer, J.L.,Hussain, T. (deposition date: 2024-02-02, release date: 2024-09-11, Last modification date: 2024-10-23)

Primary citation

Villamayor-Belinchon, L.,Sharma, P.,Gordiyenko, Y.,Llacer, J.L.,Hussain, T.
Structural basis of AUC codon discrimination during translation initiation in yeast.
Nucleic Acids Res., 52:11317-11335, 2024

PubMed Abstract: In eukaryotic translation initiation, the 48S preinitiation complex (PIC) scans the 5' untranslated region of mRNAs to search for the cognate start codon (AUG) with assistance from various eukaryotic initiation factors (eIFs). Cognate start codon recognition is precise, rejecting near-cognate codons with a single base difference. However, the structural basis of discrimination of near-cognate start codons was not known. We have captured multiple yeast 48S PICs with a near-cognate AUC codon at the P-site, revealing that the AUC codon induces instability in the codon-anticodon at the P-site, leading to a disordered N-terminal tail of eIF1A. Following eIF1 dissociation, the N-terminal domain of eIF5 fails to occupy the vacant eIF1 position, and eIF2β becomes flexible. Consequently, 48S with an AUC codon is less favourable for initiation. Furthermore, we observe hitherto unreported metastable states of the eIF2-GTP-Met-tRNAMet ternary complex, where the eIF2β helix-turn-helix domain may facilitate eIF5 association by preventing eIF1 rebinding to 48S PIC. Finally, a swivelled head conformation of 48S PIC appears crucial for discriminating incorrect and selection of the correct codon-anticodon pair during translation initiation.

PubMed: 39193907
DOI: 10.1093/nar/gkae737

Experimental method

ELECTRON MICROSCOPY (3.35 Å)