8s8f

Structure of a yeast 48S-AUC preinitiation complex in closed conformation (model py48S-AUC-3.2)

spinqualitylabelsall models 8s8f, resolution 3.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8s8f is a 10 chain structure with sequence from Kluyveromyces lactis NRRL Y-1140. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.95Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6CNL2_KLULA Publication Abstract from PubMed 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 eIF2beta 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 eIF2beta 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. Structural basis of AUC codon discrimination during translation initiation in yeast.,Villamayor-Belinchon L, Sharma P, Gordiyenko Y, Llacer JL, Hussain T Nucleic Acids Res. 2024 Aug 28:gkae737. doi: 10.1093/nar/gkae737. PMID:39193907 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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