[English] 日本語
Yorodumi
- EMDB-48514: Cryo-EM structure of VCP/p97 and VCPIP1 (VCIP135) in the presence... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-48514
TitleCryo-EM structure of VCP/p97 and VCPIP1 (VCIP135) in the presence of AMPPNP
Map dataStructure of VCP/p97 and VCPIP1 (VCIP135) in the presence of AMPPNP
Sample
  • Complex: Complex of VCP/p97 and VCPIP1/VCIP135 in the presence of AMPPNP
    • Protein or peptide: Transitional endoplasmic reticulum ATPase
    • Protein or peptide: Deubiquitinating protein VCPIP1
  • Ligand: ADENOSINE-5'-DIPHOSPHATE
  • Ligand: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER
KeywordsATPase / unfoldase / deubiquitinase / HYDROLASE
Function / homology
Function and homology information


protein K11-linked deubiquitination / endoplasmic reticulum membrane fusion / Golgi reassembly / protein K48-linked deubiquitination / : / flavin adenine dinucleotide catabolic process / VCP-NSFL1C complex / endosome to lysosome transport via multivesicular body sorting pathway / endoplasmic reticulum stress-induced pre-emptive quality control / BAT3 complex binding ...protein K11-linked deubiquitination / endoplasmic reticulum membrane fusion / Golgi reassembly / protein K48-linked deubiquitination / : / flavin adenine dinucleotide catabolic process / VCP-NSFL1C complex / endosome to lysosome transport via multivesicular body sorting pathway / endoplasmic reticulum stress-induced pre-emptive quality control / BAT3 complex binding / cellular response to arsenite ion / protein-DNA covalent cross-linking repair / Derlin-1 retrotranslocation complex / positive regulation of protein K63-linked deubiquitination / cytoplasm protein quality control / positive regulation of oxidative phosphorylation / : / Golgi stack / aggresome assembly / deubiquitinase activator activity / mitotic spindle disassembly / ubiquitin-modified protein reader activity / regulation of protein localization to chromatin / VCP-NPL4-UFD1 AAA ATPase complex / cellular response to misfolded protein / negative regulation of protein localization to chromatin / positive regulation of mitochondrial membrane potential / vesicle-fusing ATPase / K48-linked polyubiquitin modification-dependent protein binding / regulation of aerobic respiration / retrograde protein transport, ER to cytosol / stress granule disassembly / ATPase complex / regulation of synapse organization / ubiquitin-specific protease binding / positive regulation of ATP biosynthetic process / MHC class I protein binding / ubiquitin-like protein ligase binding / RHOH GTPase cycle / polyubiquitin modification-dependent protein binding / protein deubiquitination / autophagosome maturation / negative regulation of hippo signaling / endoplasmic reticulum to Golgi vesicle-mediated transport / HSF1 activation / translesion synthesis / interstrand cross-link repair / ATP metabolic process / endoplasmic reticulum unfolded protein response / proteasomal protein catabolic process / Protein methylation / Attachment and Entry / ERAD pathway / lipid droplet / proteasome complex / viral genome replication / Josephin domain DUBs / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / negative regulation of smoothened signaling pathway / macroautophagy / positive regulation of protein-containing complex assembly / Hh mutants are degraded by ERAD / establishment of protein localization / Hedgehog ligand biogenesis / Defective CFTR causes cystic fibrosis / positive regulation of non-canonical NF-kappaB signal transduction / Translesion Synthesis by POLH / ADP binding / ABC-family proteins mediated transport / autophagy / cytoplasmic stress granule / Aggrephagy / positive regulation of protein catabolic process / azurophil granule lumen / KEAP1-NFE2L2 pathway / Ovarian tumor domain proteases / positive regulation of canonical Wnt signaling pathway / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / double-strand break repair / E3 ubiquitin ligases ubiquitinate target proteins / site of double-strand break / cellular response to heat / Neddylation / ubiquitin-dependent protein catabolic process / secretory granule lumen / protein phosphatase binding / regulation of apoptotic process / ficolin-1-rich granule lumen / proteasome-mediated ubiquitin-dependent protein catabolic process / ubiquitinyl hydrolase 1 / Attachment and Entry / cysteine-type deubiquitinase activity / protein ubiquitination / ciliary basal body / endoplasmic reticulum lumen / protein domain specific binding / DNA repair / intracellular membrane-bounded organelle / DNA damage response / ubiquitin protein ligase binding
Similarity search - Function
Deubiquitinating protein VCPIP1 / Deubiquitinating protein VCPIP1, N-terminal / VCIP135 N-terminal / : / OTU1, UBXL domain / OTU-like cysteine protease / OTU domain / OTU domain profile. / AAA ATPase, CDC48 family / Cell division protein 48 (CDC48), N-terminal domain ...Deubiquitinating protein VCPIP1 / Deubiquitinating protein VCPIP1, N-terminal / VCIP135 N-terminal / : / OTU1, UBXL domain / OTU-like cysteine protease / OTU domain / OTU domain profile. / AAA ATPase, CDC48 family / Cell division protein 48 (CDC48), N-terminal domain / : / CDC48, N-terminal subdomain / Cell division protein 48 (CDC48) N-terminal domain / CDC48, domain 2 / Cell division protein 48 (CDC48), domain 2 / Cell division protein 48 (CDC48) domain 2 / CDC48 domain 2-like superfamily / Aspartate decarboxylase-like domain superfamily / AAA ATPase, AAA+ lid domain / AAA+ lid domain / ATPase, AAA-type, conserved site / AAA-protein family signature. / ATPase family associated with various cellular activities (AAA) / ATPase, AAA-type, core / Ubiquitin-like domain superfamily / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Transitional endoplasmic reticulum ATPase / Deubiquitinating protein VCPIP1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsVostal LE / Kapoor TM
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM130234 United States
CitationJournal: J Cell Biol / Year: 2025
Title: Structural insights into the coupling between VCP, an essential unfoldase, and a deubiquitinase.
Authors: Lauren E Vostal / Noa E Dahan / Matthew J Reynolds / Lily I Kronenberg / Tarun M Kapoor /
Abstract: Proteostasis involves degradation and recycling of proteins from organelles, membranes, and multiprotein complexes. These processes can depend on protein extraction and unfolding by the essential ...Proteostasis involves degradation and recycling of proteins from organelles, membranes, and multiprotein complexes. These processes can depend on protein extraction and unfolding by the essential mechanoenzyme valosin-containing protein (VCP) and on ubiquitin chain remodeling by ubiquitin-specific proteases known as deubiquitinases (DUBs). How the activities of VCP and DUBs are coordinated is poorly understood. Here, we focus on the DUB VCPIP1, a VCP interactor required for post-mitotic Golgi and ER organization. We determine ∼3.3 Å cryogenic electron microscopy structures of VCP-VCPIP1 complexes in the absence of added nucleotide or the presence of an ATP analog. We find that up to 3 VCPIP1 protomers interact with the VCP hexamer to position VCPIP1's catalytic domain at the exit of VCP's central pore, poised to cleave ubiquitin following substrate unfolding. We observe competition between VCPIP1 and other cofactors for VCP binding and show that VCP stimulates VCPIP1's DUB activity. Together, our data suggest how the two enzyme activities can be coordinated to regulate proteostasis.
History
DepositionJan 2, 2025-
Header (metadata) releaseMar 26, 2025-
Map releaseMar 26, 2025-
UpdateMay 21, 2025-
Current statusMay 21, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_48514.png

Downloads & links

-
Map

FileDownload / File: emd_48514.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationStructure of VCP/p97 and VCPIP1 (VCIP135) in the presence of AMPPNP
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 360 pix.
= 304.92 Å		0.85 Å/pix.
x 360 pix.
= 304.92 Å		0.85 Å/pix.
x 360 pix.
= 304.92 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.847 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.00333
Minimum - Maximum-0.011831824 - 0.025296362
Average (Standard dev.)0.000030492418 (±0.0006232504)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 304.92 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: Half Map B

Fileemd_48514_half_map_1.map
AnnotationHalf Map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half Map A

Fileemd_48514_half_map_2.map
AnnotationHalf Map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Complex of VCP/p97 and VCPIP1/VCIP135 in the presence of AMPPNP

EntireName: Complex of VCP/p97 and VCPIP1/VCIP135 in the presence of AMPPNP
Components
  • Complex: Complex of VCP/p97 and VCPIP1/VCIP135 in the presence of AMPPNP
    • Protein or peptide: Transitional endoplasmic reticulum ATPase
    • Protein or peptide: Deubiquitinating protein VCPIP1
  • Ligand: ADENOSINE-5'-DIPHOSPHATE
  • Ligand: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER

-
Supramolecule #1: Complex of VCP/p97 and VCPIP1/VCIP135 in the presence of AMPPNP

SupramoleculeName: Complex of VCP/p97 and VCPIP1/VCIP135 in the presence of AMPPNP
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Transitional endoplasmic reticulum ATPase

MacromoleculeName: Transitional endoplasmic reticulum ATPase / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: vesicle-fusing ATPase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 89.43682 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MASGADSKGD DLSTAILKQK NRPNRLIVDE AINEDNSVVS LSQPKMDELQ LFRGDTVLLK GKKRREAVCI VLSDDTCSDE KIRMNRVVR NNLRVRLGDV ISIQPCPDVK YGKRIHVLPI DDTVEGITGN LFEVYLKPYF LEAYRPIRKG DIFLVRGGMR A VEFKVVET ...String:
MASGADSKGD DLSTAILKQK NRPNRLIVDE AINEDNSVVS LSQPKMDELQ LFRGDTVLLK GKKRREAVCI VLSDDTCSDE KIRMNRVVR NNLRVRLGDV ISIQPCPDVK YGKRIHVLPI DDTVEGITGN LFEVYLKPYF LEAYRPIRKG DIFLVRGGMR A VEFKVVET DPSPYCIVAP DTVIHCEGEP IKREDEEESL NEVGYDDIGG CRKQLAQIKE MVELPLRHPA LFKAIGVKPP RG ILLYGPP GTGKTLIARA VANETGAFFF LINGPEIMSK LAGESESNLR KAFEEAEKNA PAIIFIDELD AIAPKREKTH GEV ERRIVS QLLTLMDGLK QRAHVIVMAA TNRPNSIDPA LRRFGRFDRE VDIGIPDATG RLEILQIHTK NMKLADDVDL EQVA NETHG HVGADLAALC SEAALQAIRK KMDLIDLEDE TIDAEVMNSL AVTMDDFRWA LSQSNPSALR ETVVEVPQVT WEDIG GLED VKRELQELVQ YPVEHPDKFL KFGMTPSKGV LFYGPPGCGK TLLAKAIANE CQANFISIKG PELLTMWFGE SEANVR EIF DKARQAAPCV LFFDELDSIA KARGGNIGDG GGAADRVINQ ILTEMDGMST KKNVFIIGAT NRPDIIDPAI LRPGRLD QL IYIPLPDEKS RVAILKANLR KSPVAKDVDL EFLAKMTNGF SGADLTEICQ RACKLAIRES IESEIRRERE RQTNPSAM E VEEDDPVPEI RRDHFEEAMR FARRSVSDND IRKYEMFAQT LQQSRGFGSF RFPSGNQGGA GPSQGSGGGT GGSVYTEDN DDDLYG

UniProtKB: Transitional endoplasmic reticulum ATPase

-
Macromolecule #2: Deubiquitinating protein VCPIP1

MacromoleculeName: Deubiquitinating protein VCPIP1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: ubiquitinyl hydrolase 1
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 134.502484 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MSQPPPPPPP LPPPPPPPEA PQTPSSLASA AASGGLLKRR DRRILSGSCP DPKCQARLFF PASGSVSIEC TECGQRHEQQ QLLGVEEVT DPDVVLHNLL RNALLGVTGA PKKNTELVKV MGLSNYHCKL LSPILARYGM DKQTGRAKLL RDMNQGELFD C ALLGDRAF ...String:
MSQPPPPPPP LPPPPPPPEA PQTPSSLASA AASGGLLKRR DRRILSGSCP DPKCQARLFF PASGSVSIEC TECGQRHEQQ QLLGVEEVT DPDVVLHNLL RNALLGVTGA PKKNTELVKV MGLSNYHCKL LSPILARYGM DKQTGRAKLL RDMNQGELFD C ALLGDRAF LIEPEHVNTV GYGKDRSGSL LYLHDTLEDI KRANKSQECL IPVHVDGDGH CLVHAVSRAL VGRELFWHAL RE NLKQHFQ QHLARYQALF HDFIDAAEWE DIINECDPLF VPPEGVPLGL RNIHIFGLAN VLHRPIILLD SLSGMRSSGD YSA TFLPGL IPAEKCTGKD GHLNKPICIA WSSSGRNHYI PLVGIKGAAL PKLPMNLLPK AWGVPQDLIK KYIKLEEDGG CVIG GDRSL QDKYLLRLVA AMEEVFMDKH GIHPSLVADV HQYFYRRTGV IGVQPEEVTA AAKKAVMDNR LHKCLLCGAL SELHV PPEW LAPGGKLYNL AKSTHGQLRT DKNYSFPLNN LVCSYDSVKD VLVPDYGMSN LTACNWCHGT SVRKVRGDGS IVYLDG DRT NSRSTGGKCG CGFKHFWDGK EYDNLPEAFP ITLEWGGRVV RETVYWFQYE SDSSLNSNVY DVAMKLVTKH FPGEFGS EI LVQKVVHTIL HQTAKKNPDD YTPVNIDGAH AQRVGDVQGQ ESESQLPTKI ILTGQKTKTL HKEELNMSKT ERTIQQNI T EQASVMQKRK TEKLKQEQKG QPRTVSPSTI RDGPSSAPAT PTKAPYSPTT SKEKKIRITT NDGRQSMVTL KSSTTFFEL QESIAREFNI PPYLQCIRYG FPPKELMPPQ AGMEKEPVPL QHGDRITIEI LKSKAEGGQS AAAHSAHTVK QEDIAVTGKL SSKELQEQA EKEMYSLCLL ATLMGEDVWS YAKGLPHMFQ QGGVFYSIMK KTMGMADGKH CTFPHLPGKT FVYNASEDRL E LCVDAAGH FPIGPDVEDL VKEAVSQVRA EATTRSRESS PSHGLLKLGS GGVVKKKSEQ LHNVTAFQGK GHSLGTASGN PH LDPRARE TSVVRKHNTG TDFSNSSTKT EPSVFTASSS NSELIRIAPG VVTMRDGRQL DPDLVEAQRK KLQEMVSSIQ ASM DRHLRD QSTEQSPSDL PQRKTEVVSS SAKSGSLQTG LPESFPLTGG TENLNTETTD GCVADALGAA FATRSKAQRG NSVE ELEEM DSQDAEMTNT TEPMDHS

UniProtKB: Deubiquitinating protein VCPIP1

-
Macromolecule #3: ADENOSINE-5'-DIPHOSPHATE

MacromoleculeName: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 3 / Number of copies: 2 / Formula: ADP
Molecular weightTheoretical: 427.201 Da
Chemical component information

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

-
Macromolecule #4: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER

MacromoleculeName: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / type: ligand / ID: 4 / Number of copies: 2 / Formula: ANP
Molecular weightTheoretical: 506.196 Da
Chemical component information

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
Component:
ConcentrationFormulaName
50.0 mMC8H18N2O4SHEPES
25.0 mMKClPotassium chloride
2.5 mMMgCl2Magnesium chloride
2.5 mMC10H17N3O6SGlutathione
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average exposure time: 1.6 sec. / Average electron dose: 44.6 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Details: Ab initio reconstruction as implemented in cryoSPARC
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 47000
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more