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- PDB-9r86: Major Vault Protein from Human Brain -

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Basic information

Entry
Database: PDB / ID: 9r86
TitleMajor Vault Protein from Human Brain
ComponentsMajor vault protein
KeywordsSTRUCTURAL PROTEIN / Complex / Vault / large protein
Function / homology
Function and homology information


negative regulation of protein tyrosine kinase activity / protein activation cascade / negative regulation of protein autophosphorylation / ERBB signaling pathway / negative regulation of epidermal growth factor receptor signaling pathway / mRNA transport / nuclear pore / protein transport / secretory granule lumen / protein phosphatase binding ...negative regulation of protein tyrosine kinase activity / protein activation cascade / negative regulation of protein autophosphorylation / ERBB signaling pathway / negative regulation of epidermal growth factor receptor signaling pathway / mRNA transport / nuclear pore / protein transport / secretory granule lumen / protein phosphatase binding / ficolin-1-rich granule lumen / cytoskeleton / cell population proliferation / ribonucleoprotein complex / Neutrophil degranulation / protein kinase binding / perinuclear region of cytoplasm / extracellular exosome / extracellular region / identical protein binding / nucleus / membrane / cytoplasm / cytosol
Similarity search - Function
Major vault protein, N-terminal / Major vault protein, shoulder domain / Major vault protein / Major vault protein repeat domain 3 / Major vault protein repeat domain 2 / Major vault protein repeat domain 4 / Major vault protein repeat domain / Major vault protein repeat domain superfamily / Major vault protein repeat domain 2 superfamily / Major Vault Protein repeat domain ...Major vault protein, N-terminal / Major vault protein, shoulder domain / Major vault protein / Major vault protein repeat domain 3 / Major vault protein repeat domain 2 / Major vault protein repeat domain 4 / Major vault protein repeat domain / Major vault protein repeat domain superfamily / Major vault protein repeat domain 2 superfamily / Major Vault Protein repeat domain / Shoulder domain / Major Vault Protein repeat domain / Major Vault Protein Repeat domain / Major Vault Protein repeat domain / MVP (vault) repeat profile. / Band 7/SPFH domain superfamily
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsLovestam, S.L. / Scheres, S.H.W.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom) United Kingdom
CitationJournal: Structure / Year: 2025
Title: Cryo-EM structure of the vault from human brain reveals symmetry mismatch at its caps.
Authors: Sofia Lövestam / Sjors H W Scheres /
Abstract: The vault protein is expressed in most eukaryotic cells, where it is assembled on polyribosomes into large hollow barrel-shaped complexes. Despite its widespread and abundant presence in cells, the ...The vault protein is expressed in most eukaryotic cells, where it is assembled on polyribosomes into large hollow barrel-shaped complexes. Despite its widespread and abundant presence in cells, the biological function of the vault remains unclear. In this study, we describe the cryo-EM structure of vault particles that were imaged as a contamination of a preparation to extract tau filaments from brain tissue of an individual with progressive supranuclear palsy (PSP). We identify a mechanism of symmetry mismatch at the caps of the vault, from 39-fold to 13-fold symmetry, where two out of three monomers are sequentially excluded from the cap, resulting in a narrow, greasy pore at the tip of the vault. Our structure offers valuable insights for engineering carboxy-terminal modifications of the major vault protein (MVP) for potential therapeutic applications.
History
DepositionMay 15, 2025Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 2, 2025Provider: repository / Type: Initial release
Revision 1.0Jul 2, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jul 2, 2025Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jul 2, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 2, 2025Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 2, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jul 2, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Aug 27, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
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Revision 1.2Oct 15, 2025Group: Data collection / Database references / Category: citation / em_admin
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A0: Major vault protein
A1: Major vault protein
A2: Major vault protein
A3: Major vault protein
A4: Major vault protein
A5: Major vault protein
A6: Major vault protein
A7: Major vault protein
A8: Major vault protein
A9: Major vault protein
Ac: Major vault protein
Ad: Major vault protein
Ae: Major vault protein
Af: Major vault protein
Ag: Major vault protein
Ah: Major vault protein
Ai: Major vault protein
Aj: Major vault protein
Ak: Major vault protein
Al: Major vault protein
Am: Major vault protein
An: Major vault protein
Ap: Major vault protein
Aq: Major vault protein
Ar: Major vault protein
As: Major vault protein
At: Major vault protein
Au: Major vault protein
Av: Major vault protein
Aw: Major vault protein
Ax: Major vault protein
Ay: Major vault protein
Az: Major vault protein
BA: Major vault protein
BB: Major vault protein
BC: Major vault protein
BD: Major vault protein
BE: Major vault protein
BF: Major vault protein


Theoretical massNumber of molelcules
Total (without water)3,878,65839
Polymers3,878,65839
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein ...
Major vault protein / MVP / Lung resistance-related protein


Mass: 99452.766 Da / Num. of mol.: 39 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q14764
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Major Vault Protein / Type: COMPLEX / Entity ID: all / Source: NATURAL
Source (natural)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 5000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 40 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k)

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Processing

EM softwareName: RELION / Version: 5 / Category: image acquisition / Details: solves big structures
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 7367 / Algorithm: BACK PROJECTION / Symmetry type: POINT

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