8p09

48S late-stage initiation complex with non methylated mRNA

spinqualitylabelsall models 8p09, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8p09 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. Method: Electron Microscopy, Resolution 3.3Å Ligands: I2T, MG, T6A Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The most abundant N(6)-methyladenosine (m(6)A) modification on mRNAs is installed non-stoichiometrically across transcripts, with 5' untranslated regions (5' UTRs) being the least conductive. 5' UTRs are essential for translation initiation, yet the molecular mechanisms orchestrated by m(6)A remain poorly understood. Here, we combined structural, biochemical, and single-molecule approaches and show that at the most common position, a single m(6)A does not affect translation yields, the kinetics of translation initiation complex assembly, or start codon recognition both under permissive growth and following exposure to oxidative stress. Cryoelectron microscopy (cryo-EM) structures of the late preinitiation complex reveal that m(6)A purine ring established stacking interactions with an arginine side chain of the initiation factor eIF2alpha, although with only a marginal energy contribution, as estimated computationally. These findings provide molecular insights into m(6)A interactions with the initiation complex and suggest that the subtle stabilization is unlikely to affect the translation dynamics under homeostatic conditions or stress. N(6)-methyladenosine in 5' UTR does not promote translation initiation.,Guca E, Alarcon R, Palo MZ, Santos L, Alonso-Gil S, Davyt M, de Lima LHF, Boissier F, Das S, Zagrovic B, Puglisi JD, Hashem Y, Ignatova Z Mol Cell. 2024 Feb 1;84(3):584-595.e6. doi: 10.1016/j.molcel.2023.12.028. Epub , 2024 Jan 19. PMID:38244546 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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