9ru9 | pdb_00009ru9

RPS26dC HEK mutant 80S ribosome bound to Kozak mRNA (RPS26dC-Kozak)

spinqualitylabelsall models 9ru9, resolution 2.97Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ru9 is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.97Å Ligands: 1MA, 4AC, 4SU, 5MC, 6MZ, A2M, AME, ANM, B8N, G7M, H2U, HIC, HY3, HYG, K, M3L, MA6, MET, MG, MLZ, NA, OMC, OMG, OMU, PSU, SAC, UR3, UY1, V5N, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL22_HUMAN Publication Abstract from PubMed The ribosome mRNA channel is central to translation, yet its role in regulatory mechanisms remains unclear. Using cryo-EM of human ribosomal complexes bound to Kozak and TISU mRNAs from wild-type (WT) and RPS26/eS26 mutant (RPS26dC) cells, we demonstrate that both RPS26/eS26 and mRNA adopt distinct conformations, explaining the opposing effects of RPS26dC on their activity. Translatome studies of WT and RPS26dC reveal AUG-context-dependent changes in 48S and 80S initiation complexes and slower scanning. Downregulated mRNAs are enriched for specific AUG-upstream nucleotides and a -1-cytosine contacting 18S rRNA G1207, an interaction lost in RPS26dC. Strongly affected transcripts include replication-dependent histones, which, despite short 5'UTRs and suboptimal Kozak, exhibit robust translation activity that is RPS26/eS26-dependent. We identify a translational enhancer in the H2B 5'UTR (-16 to -9) overlapping predicted RPS26/eS26-binding sites, with a distinct ribosome-bound conformation. Exploiting these features, we engineered a high-efficiency translational cassette with minimal leaky scanning. These findings underscore the role of the ribosome's mRNA channel in selective translation and its therapeutic potential. Structural and molecular basis of specialized translation mediated by the ribosome mRNA-binding channel.,Fraticelli D, Hiregange DG, Weiss B, Ogran A, Havkin-Solomon T, Roman IM, Bashan A, Yonath A, Dikstein R Nat Commun. 2026 Apr 29. doi: 10.1038/s41467-026-72263-5. PMID:42056121 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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