9gy4

60S ribosomal subunit in complex with E3-UFM1 ligase and RQC machinery components NEMF and LTN1 (Composite map)

spinqualitylabelsall models 9gy4, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9gy4 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: MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CK5P3_HUMAN Substrate adapter of E3 ligase complexes mediating ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, and which is involved in various processes, such as ribosome recycling and reticulophagy (also called ER-phagy) (PubMed:23152784, PubMed:30635284, PubMed:32851973, PubMed:36121123, PubMed:36543799, PubMed:37595036, PubMed:38383785, PubMed:38383789). As part of the UREL complex, plays a key role in ribosome recycling by promoting mono-ufmylation of RPL26/uL24 subunit of the 60S ribosome (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 occurs on free 60S ribosomes following ribosome dissociation: it weakens the junction between post-termination 60S subunits and SEC61 translocons, promoting release and recycling of the large ribosomal subunit from the endoplasmic reticulum membrane (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 and subsequent 60S ribosome recycling either take place after normal termination of translation or after ribosome stalling during cotranslational translocation at the endoplasmic reticulum (PubMed:32851973, PubMed:37595036, PubMed:38383785, PubMed:38383789). Within the UREL complex, CDK5RAP3 acts as a substrate adapter that constrains UFL1 ligase activity to mono-ufmylate RPL26/uL24 at 'Lys-134' (PubMed:36121123, PubMed:38383785, PubMed:38383789). The UREL complex is also involved in reticulophagy in response to endoplasmic reticulum stress by promoting ufmylation of proteins such as CYB5R3, thereby promoting lysosomal degradation of ufmylated proteins (PubMed:36543799). Also acts as a regulator of transcription: negatively regulates NF-kappa-B-mediated gene transcription through the control of RELA phosphorylation (PubMed:17785205, PubMed:20228063). Also regulates mitotic G2/M transition checkpoint and mitotic G2 DNA damage checkpoint (PubMed:15790566, PubMed:19223857). Through its interaction with CDKN2A/ARF and MDM2 may induce MDM2-dependent p53/TP53 ubiquitination, stabilization and activation in the nucleus, thereby promoting G1 cell cycle arrest and inhibition of cell proliferation (PubMed:16173922). May also play a role in the rupture of the nuclear envelope during apoptosis (PubMed:23478299). May regulate MAPK14 activity by regulating its dephosphorylation by PPM1D/WIP1 (PubMed:21283629). Required for liver development (By similarity).[UniProtKB:Q99LM2] (Microbial infection) May be negatively regulated by hepatitis B virus large envelope protein mutant pre-s2 to promote mitotic entry. Publication Abstract from PubMed Degradation of arrest peptides from endoplasmic reticulum (ER) translocon-bound 60S ribosomal subunits via the ribosome-associated quality control (ER-RQC) pathway requires covalent modification of RPL26/uL24 on 60S ribosomal subunits with UFM1. However, the underlying mechanism that coordinates the UFMylation and RQC pathways remains elusive. Structural analysis of ER-RQC intermediates revealed concomitant binding and direct interaction of the UFMylation and RQC machineries on the 60S. In the presence of an arrested peptidyl-transfer RNA, the RQC factor NEMF and the UFM1 E3 ligase (E3(UFM1)) form a direct interaction via the UFL1 subunit of E3(UFM1), and UFL1 adopts a conformation distinct from that previously observed for posttermination 60S. While this concomitant binding occurs on translocon-bound 60S, LTN1 recruitment and arrest peptide degradation require UFMylation-dependent 60S dissociation from the translocon. These data reveal a mechanism by which the UFMylation cycle orchestrates ER-RQC. UFMylation orchestrates spatiotemporal coordination of RQC at the ER.,Penchev I, Gumbin S, Scavone F, Berninghausen O, Becker T, Kopito R, Beckmann R Sci Adv. 2025 May 2;11(18):eadv0435. doi: 10.1126/sciadv.adv0435. Epub 2025 May , 2. PMID:40315331 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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