View source for 9mpt


==Cryo-EM structure of VCPIP1 UBX domain bound to VCP N-domain (with D1 domain)==
<StructureSection load='9mpt' size='340' side='right'caption='[[9mpt]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9mpt]] is a 2 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=9MPT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9MPT 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]] 3.1&#8491;</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=9mpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9mpt OCA], [https://pdbe.org/9mpt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9mpt RCSB], [https://www.ebi.ac.uk/pdbsum/9mpt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9mpt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VCIP1_HUMAN VCIP1_HUMAN] Deubiquitinating enzyme involved in DNA repair and reassembly of the Golgi apparatus and the endoplasmic reticulum following mitosis (PubMed:32649882). Necessary for VCP-mediated reassembly of Golgi stacks after mitosis (By similarity). Plays a role in VCP-mediated formation of transitional endoplasmic reticulum (tER) (By similarity). Mediates dissociation of the ternary complex containing STX5A, NSFL1C and VCP (By similarity). Also involved in DNA repair following phosphorylation by ATM or ATR: acts by catalyzing deubiquitination of SPRTN, thereby promoting SPRTN recruitment to chromatin and subsequent proteolytic cleavage of covalent DNA-protein cross-links (DPCs) (PubMed:32649882). Hydrolyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitin chains (PubMed:23827681).[UniProtKB:Q8CF97]<ref>PMID:23827681</ref> <ref>PMID:32649882</ref>   (Microbial infection) Regulates the duration of C.botulinum neurotoxin type A (BoNT/A) intoxication by catalyzing deubiquitination of Botulinum neurotoxin A light chain (LC), thereby preventing LC degradation by the proteasome, and accelerating botulinum neurotoxin intoxication in patients.<ref>PMID:28584101</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
VCP/p97 regulates a wide range of cellular processes, including post-mitotic Golgi reassembly. In this context, VCP is assisted by p47, an adapter protein, and VCPIP1, a deubiquitylase (DUB). However, how they organize into a functional ternary complex to promote Golgi assembly remains unknown. Here, we use cryo-EM to characterize both VCP-VCPIP1 and VCP-VCPIP1-p47 complexes. We show that VCPIP1 engages VCP through two interfaces: one involving the N-domain of VCP and the UBX domain of VCPIP1, and the other involving the VCP D2 domains and a region of VCPIP1 we refer to as VCPID. The p47 UBX domain competitively binds to the VCP N-domain, while not affecting VCPID binding. We show that VCPID is critical for VCP-mediated enhancement of DUB activity and proper Golgi assembly. The ternary structure along with biochemical and cellular data provides new insights into the complex interplay of VCP with its co-factors.

Structural basis of VCP-VCPIP1-p47 ternary complex in Golgi maintenance.,Shah B, Hunkeler M, Bratt A, Yue H, Jaen Maisonet I, Fischer ES, Buhrlage SJ Nat Commun. 2025 Aug 28;16(1):8025. doi: 10.1038/s41467-025-63161-3. PMID:40877265<ref>PMID:40877265</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9mpt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Buhrlage SJ]]
[[Category: Fischer ES]]
[[Category: Hunkeler M]]
[[Category: Shah B]]