View source for 9gy4


==60S ribosomal subunit in complex with E3-UFM1 ligase and RQC machinery components NEMF and LTN1 (Composite map)==
<StructureSection load='9gy4' size='340' side='right'caption='[[9gy4]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9gy4]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9GY4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9GY4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9gy4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9gy4 OCA], [https://pdbe.org/9gy4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9gy4 RCSB], [https://www.ebi.ac.uk/pdbsum/9gy4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9gy4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CK5P3_HUMAN 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]<ref>PMID:15790566</ref> <ref>PMID:16173922</ref> <ref>PMID:17785205</ref> <ref>PMID:19223857</ref> <ref>PMID:20228063</ref> <ref>PMID:21283629</ref> <ref>PMID:23152784</ref> <ref>PMID:23478299</ref> <ref>PMID:30635284</ref> <ref>PMID:32851973</ref> <ref>PMID:36121123</ref> <ref>PMID:36543799</ref> <ref>PMID:37595036</ref> <ref>PMID:38383785</ref> <ref>PMID:38383789</ref>   (Microbial infection) May be negatively regulated by hepatitis B virus large envelope protein mutant pre-s2 to promote mitotic entry.<ref>PMID:21971960</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:40315331</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9gy4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Becker T]]
[[Category: Beckmann R]]
[[Category: Gumbin S]]
[[Category: Kopito R]]
[[Category: Penchev I]]