7ucj | pdb_00007ucj

Mammalian 80S translation initiation complex with mRNA and Harringtonine

spinqualitylabelsall models 7ucj, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ucj is a 10 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1MA, 2MG, 4AC, 5MC, 5MU, 6MZ, 7MG, A2M, B8H, B8K, B8N, B8Q, B8T, B8W, B9B, B9H, BGH, E6G, E7G, I4U, M7A, MA6, MG, MHG, MLZ, MMX, MQ6, N, OMC, OMG, OMU, P4U, P7G, PSU, T6A, UR3, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [G1TT27_RABIT] Publication Abstract from PubMed mRNA function is influenced by modifications that modulate canonical nucleobase behavior. We show that a single modification mediates distinct impacts on mRNA translation in a position-dependent manner. Although cytidine acetylation (ac4C) within protein-coding sequences stimulates translation, ac4C within 5' UTRs impacts protein synthesis at the level of initiation. 5' UTR acetylation promotes initiation at upstream sequences, competitively inhibiting annotated start codons. Acetylation further directly impedes initiation at optimal AUG contexts: ac4C within AUG-flanking Kozak sequences reduced initiation in base-resolved transcriptome-wide HeLa results and in vitro utilizing substrates with site-specific ac4C incorporation. Cryo-EM of mammalian 80S initiation complexes revealed that ac4C in the -1 position adjacent to an AUG start codon disrupts an interaction between C and hypermodified t6A at nucleotide 37 of the initiator tRNA. These findings demonstrate the impact of RNA modifications on nucleobase function at a molecular level and introduce mRNA acetylation as a factor regulating translation in a location-specific manner. Direct epitranscriptomic regulation of mammalian translation initiation through N4-acetylcytidine.,Arango D, Sturgill D, Yang R, Kanai T, Bauer P, Roy J, Wang Z, Hosogane M, Schiffers S, Oberdoerffer S Mol Cell. 2022 Aug 4;82(15):2797-2814.e11. doi: 10.1016/j.molcel.2022.05.016., Epub 2022 Jun 8. PMID:35679869 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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