9mpv

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of three VCPIP1 VCPIDs bound to VCP

Structural highlights

9mpv is a 9 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 3.1Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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]^[1] ^[2] (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.^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mevissen TE, Hospenthal MK, Geurink PP, Elliott PR, Akutsu M, Arnaudo N, Ekkebus R, Kulathu Y, Wauer T, El Oualid F, Freund SM, Ovaa H, Komander D. OTU Deubiquitinases Reveal Mechanisms of Linkage Specificity and Enable Ubiquitin Chain Restriction Analysis. Cell. 2013 Jul 3;154(1):169-84. doi: 10.1016/j.cell.2013.05.046. PMID:23827681 doi:10.1016/j.cell.2013.05.046
↑ Huang J, Zhou Q, Gao M, Nowsheen S, Zhao F, Kim W, Zhu Q, Kojima Y, Yin P, Zhang Y, Guo G, Tu X, Deng M, Luo K, Qin B, Machida Y, Lou Z. Tandem Deubiquitination and Acetylation of SPRTN Promotes DNA-Protein Crosslink Repair and Protects against Aging. Mol Cell. 2020 Sep 3;79(5):824-835.e5. PMID:32649882 doi:10.1016/j.molcel.2020.06.027
↑ Tsai YC, Kotiya A, Kiris E, Yang M, Bavari S, Tessarollo L, Oyler GA, Weissman AM. Deubiquitinating enzyme VCIP135 dictates the duration of botulinum neurotoxin type A intoxication. Proc Natl Acad Sci U S A. 2017 Jun 27;114(26):E5158-E5166. PMID:28584101 doi:10.1073/pnas.1621076114
↑ Shah B, Hunkeler M, Bratt A, Yue H, Jaen Maisonet I, Fischer ES, Buhrlage SJ. Structural basis of VCP-VCPIP1-p47 ternary complex in Golgi maintenance. Nat Commun. 2025 Aug 28;16(1):8025. PMID:40877265 doi:10.1038/s41467-025-63161-3

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9mpv"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9mpv is ON HOLD
+==Cryo-EM structure of three VCPIP1 VCPIDs bound to VCP==
+<StructureSection load='9mpv' size='340' side='right'caption='[[9mpv]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9mpv]] is a 9 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=9MPV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9MPV 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=9mpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9mpv OCA], [https://pdbe.org/9mpv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9mpv RCSB], [https://www.ebi.ac.uk/pdbsum/9mpv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9mpv 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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9mpv" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Buhrlage SJ]]
+[[Category: Fischer EF]]
+[[Category: Hunkeler M]]
+[[Category: Shah B]]

9mpv

From Proteopedia

Current revision

Cryo-EM structure of three VCPIP1 VCPIDs bound to VCP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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