9ru8 | pdb_00009ru8

WT-HEK 80S ribosome bound to TISU mRNA (WT-TISU)

spinqualitylabelsall models 9ru8, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ru8 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 3Å Ligands: 1MA, 4AC, 4SU, 5MC, 6MZ, A2M, B8N, G7M, H2U, HYG, K, MA6, MG, MLZ, NA, OMC, OMG, OMU, PSU, SPD, UR3, V5N, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL40_HUMAN Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. Ribosomal protein L40 is a component of the 60S subunit of the ribosome. 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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