3OJ4

Crystal structure of the A20 ZnF4, ubiquitin and UbcH5A complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.319 
  • R-Value Work: 0.280 
  • R-Value Observed: 0.284 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Ubiquitin Binding to A20 ZnF4 Is Required for Modulation of NF-κB Signaling

Bosanac, I.Wertz, I.E.Pan, B.Yu, C.Kusam, S.Lam, C.Phu, L.Phung, Q.Maurer, B.Arnott, D.Kirkpatrick, D.S.Dixit, V.M.Hymowitz, S.G.

(2010) Mol Cell 40: 548-557

  • DOI: https://doi.org/10.1016/j.molcel.2010.10.009
  • Primary Citation of Related Structures:  
    3OJ3, 3OJ4

  • PubMed Abstract: 

    Inactivating mutations in the ubiquitin (Ub) editing protein A20 promote persistent nuclear factor (NF)-κB signaling and are genetically linked to inflammatory diseases and hematologic cancers. A20 tightly regulates NF-κB signaling by acting as an Ub editor, removing K63-linked Ub chains and mediating addition of Ub chains that target substrates for degradation. However, a precise molecular understanding of how A20 modulates this pathway remains elusive. Here, using structural analysis, domain mapping, and functional assays, we show that A20 zinc finger 4 (ZnF4) does not directly interact with E2 enzymes but instead can bind mono-Ub and K63-linked poly-Ub. Mutations to the A20 ZnF4 Ub-binding surface result in decreased A20-mediated ubiquitination and impaired regulation of NF-κB signaling. Collectively, our studies illuminate the mechanistically distinct but biologically interdependent activities of the A20 ZnF and ovarian tumor (OTU) domains that are inherent to the Ub editing process and, ultimately, to regulation of NF-κB signaling.


  • Organizational Affiliation

    Department of Structural Biology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ubiquitin-conjugating enzyme E2 D1
A, D
153Homo sapiensMutation(s): 0 
Gene Names: UBE2D1SFTUBC5AUBCH5UBCH5A
EC: 6.3.2.19
UniProt & NIH Common Fund Data Resources
Find proteins for P51668 (Homo sapiens)
Explore P51668 
Go to UniProtKB:  P51668
PHAROS:  P51668
GTEx:  ENSG00000072401 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP51668
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Ubiquitin
B, E
79Homo sapiensMutation(s): 0 
Gene Names: UBB
UniProt & NIH Common Fund Data Resources
Find proteins for P0CG48 (Homo sapiens)
Explore P0CG48 
Go to UniProtKB:  P0CG48
PHAROS:  P0CG48
GTEx:  ENSG00000150991 
Entity Groups  
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UniProt GroupP0CG48
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Tumor necrosis factor alpha-induced protein 3
C, F
49Homo sapiensMutation(s): 0 
Gene Names: TNFAIP3OTUD7C
UniProt & NIH Common Fund Data Resources
Find proteins for P21580 (Homo sapiens)
Explore P21580 
Go to UniProtKB:  P21580
PHAROS:  P21580
GTEx:  ENSG00000118503 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP21580
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.319 
  • R-Value Work: 0.280 
  • R-Value Observed: 0.284 
  • Space Group: P 3 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 102.646α = 90
b = 102.646β = 90
c = 112.686γ = 120
Software Package:
Software NamePurpose
BOSdata collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-12-08
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2018-01-24
    Changes: Structure summary
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description