6HEM

Structure of the C-terminal domain of USP25 (748-1048)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Distinct USP25 and USP28 Oligomerization States Regulate Deubiquitinating Activity.

Gersch, M.Wagstaff, J.L.Toms, A.V.Graves, B.Freund, S.M.V.Komander, D.

(2019) Mol Cell 74: 436

  • DOI: https://doi.org/10.1016/j.molcel.2019.02.030
  • Primary Citation of Related Structures:  
    6HEH, 6HEI, 6HEJ, 6HEK, 6HEL, 6HEM

  • PubMed Abstract: 

    The evolutionarily related deubiquitinating enzymes (DUBs) USP25 and USP28 comprise an identical overall domain architecture but are functionally non-redundant: USP28 stabilizes c-MYC and other nuclear proteins, and USP25 regulates inflammatory TRAF signaling. We here compare molecular features of USP25 and USP28. Active enzymes form distinctively shaped dimers, with a dimerizing insertion spatially separating independently active catalytic domains. In USP25, but not USP28, two dimers can form an autoinhibited tetramer, where a USP25-specific, conserved insertion sequence blocks ubiquitin binding. In full-length enzymes, a C-terminal domain with a previously unknown fold has no impact on oligomerization, but N-terminal regions affect the dimer-tetramer equilibrium in vitro. We confirm oligomeric states of USP25 and USP28 in cells and show that modulating oligomerization affects substrate stabilization in accordance with in vitro activity data. Our work highlights how regions outside of the catalytic domain enable a conceptually intriguing interplay of DUB oligomerization and activity.


  • Organizational Affiliation

    Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Chemical Genomics Centre, Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany; Department of Chemistry and Chemical Biology, Technical University Dortmund, Otto-Hahn-Str. 4a, 44227 Dortmund, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ubiquitin carboxyl-terminal hydrolase 25303Homo sapiensMutation(s): 0 
Gene Names: USP25USP21
EC: 3.4.19.12
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UHP3 (Homo sapiens)
Explore Q9UHP3 
Go to UniProtKB:  Q9UHP3
PHAROS:  Q9UHP3
GTEx:  ENSG00000155313 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UHP3
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.182 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.957α = 90
b = 78.288β = 90
c = 84.909γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
AMPLEphasing
ARP/wARPmodel building
REFMACrefinement
Cootmodel building

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Medical Research Council (United Kingdom)United KingdomU105192732
European Research CouncilUnited Kingdom724804

Revision History  (Full details and data files)

  • Version 1.0: 2019-03-27
    Type: Initial release
  • Version 1.1: 2019-04-10
    Changes: Data collection, Database references
  • Version 1.2: 2019-05-15
    Changes: Data collection, Database references
  • Version 1.3: 2024-05-15
    Changes: Data collection, Database references