3OSK

Crystal structure of human CTLA-4 apo homodimer


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.203 

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This is version 1.4 of the entry. See complete history


Literature

Rigid-body ligand recognition drives cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor triggering

Yu, C.Sonnen, A.F.-P.George, R.Dessailly, B.H.Stagg, L.J.Evans, E.J.Orengo, C.A.Stuart, D.I.Ladbury, J.E.Ikemizu, S.Gilbert, R.J.C.Davis, S.J.

(2011) J Biol Chem 286: 6685-6696

  • DOI: https://doi.org/10.1074/jbc.M110.182394
  • Primary Citation of Related Structures:  
    3OSK

  • PubMed Abstract: 

    The inhibitory T-cell surface-expressed receptor, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which belongs to the class of cell surface proteins phosphorylated by extrinsic tyrosine kinases that also includes antigen receptors, binds the related ligands, B7-1 and B7-2, expressed on antigen-presenting cells. Conformational changes are commonly invoked to explain ligand-induced "triggering" of this class of receptors. Crystal structures of ligand-bound CTLA-4 have been reported, but not the apo form, precluding analysis of the structural changes accompanying ligand binding. The 1.8-Å resolution structure of an apo human CTLA-4 homodimer emphasizes the shared evolutionary history of the CTLA-4/CD28 subgroup of the immunoglobulin superfamily and the antigen receptors. The ligand-bound and unbound forms of both CTLA-4 and B7-1 are remarkably similar, in marked contrast to B7-2, whose binding to CTLA-4 has elements of induced fit. Isothermal titration calorimetry reveals that ligand binding by CTLA-4 is enthalpically driven and accompanied by unfavorable entropic changes. The similarity of the thermodynamic parameters determined for the interactions of CTLA-4 with B7-1 and B7-2 suggests that the binding is not highly specific, but the conformational changes observed for B7-2 binding suggest some level of selectivity. The new structure establishes that rigid-body ligand interactions are capable of triggering CTLA-4 phosphorylation by extrinsic kinase(s).


  • Organizational Affiliation

    Nuffield Department of Clinical Medicine and MRC Human Immunology Unit, The University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cytotoxic T-lymphocyte protein 4
A, B
130Homo sapiensMutation(s): 0 
Gene Names: CD152CTLA4
UniProt & NIH Common Fund Data Resources
Find proteins for P16410 (Homo sapiens)
Explore P16410 
Go to UniProtKB:  P16410
PHAROS:  P16410
GTEx:  ENSG00000163599 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16410
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.203 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 43.864α = 90
b = 51.457β = 90
c = 102.849γ = 90
Software Package:
Software NamePurpose
HKL-3000data collection
PHASERphasing
PHENIXrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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: 2014-02-05
    Changes: Database references
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Database references, Derived calculations, Structure summary
  • Version 1.4: 2023-11-01
    Changes: Data collection, Database references, Refinement description, Structure summary