6SWS

The DBB dimerization domain of B-cell adaptor for PI3K (BCAP) is required for down regulation of inflammatory signalling through the Toll-like receptor pathway


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.198 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Negative Regulation of TLR Signaling by BCAP Requires Dimerization of Its DBB Domain.

Lauenstein, J.U.Scherm, M.J.Udgata, A.Moncrieffe, M.C.Fisher, D.I.Gay, N.J.

(2020) J Immunol 204: 2269-2276

  • DOI: https://doi.org/10.4049/jimmunol.1901210
  • Primary Citation of Related Structures:  
    6SWS

  • PubMed Abstract: 

    The B cell adaptor protein (BCAP) is a multimodular regulator of inflammatory signaling in diverse immune system cells. BCAP couples TLR signaling to phosphoinositide metabolism and inhibits MyD88-directed signal transduction. BCAP is recruited to the TLR signalosome forming multitypic interactions with the MAL and MyD88 signaling adaptors. In this study, we show that indirect dimerization of BCAP TIR is required for negative regulation of TLR signaling. This regulation is mediated by a transcription factor Ig (TIG/IPT) domain, a fold found in the NF-κB family of transcription factors. We have solved the crystal structure of the BCAP TIG and find that it is most similar to that of early B cell factor 1 (EBF1). In both cases, the dimer is stabilized by a helix-loop-helix motif at the C terminus and interactions between the β-sheets of the Ig domains. BCAP is exclusively localized in the cytosol and is unable to bind DNA. Thus, the TIG domain is a promiscuous dimerization module that has been appropriated for a range of regulatory functions in gene expression and signal transduction.


  • Organizational Affiliation

    Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom; and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphoinositide 3-kinase adapter protein 1
A, B, C, D, E
113Homo sapiensMutation(s): 0 
Gene Names: PIK3AP1BCAP
UniProt & NIH Common Fund Data Resources
Find proteins for Q6ZUJ8 (Homo sapiens)
Explore Q6ZUJ8 
Go to UniProtKB:  Q6ZUJ8
PHAROS:  Q6ZUJ8
GTEx:  ENSG00000155629 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6ZUJ8
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.198 
  • Space Group: P 43 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 87.169α = 90
b = 87.169β = 90
c = 234.075γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
SHELXDphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Wellcome TrustUnited KingdomWT100321/z/12/Z

Revision History  (Full details and data files)

  • Version 1.0: 2020-02-19
    Type: Initial release
  • Version 1.1: 2020-04-01
    Changes: Database references
  • Version 1.2: 2020-04-15
    Changes: Database references
  • Version 1.3: 2024-05-15
    Changes: Data collection, Database references, Refinement description