3OSK
Crystal structure of human CTLA-4 apo homodimer
Summary for 3OSK
Entry DOI | 10.2210/pdb3osk/pdb |
Descriptor | Cytotoxic T-lymphocyte protein 4, 2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (4 entities in total) |
Functional Keywords | beta sandwich, homodimer, immunoglobulin superfamily (beta sandwich) fold, receptor, signalling, b7-1(cd80), b7-2(cd86), membrane, immune system |
Biological source | Homo sapiens (human) |
Cellular location | Cell membrane; Single-pass type I membrane protein: P16410 |
Total number of polymer chains | 2 |
Total formula weight | 28580.48 |
Authors | Yu, C.,Sonnen, A.F.-P.,Ikemizu, S.,Stuart, D.I.,Gilbert, R.J.C.,Davis, S.J. (deposition date: 2010-09-09, release date: 2010-12-08, Last modification date: 2024-10-30) |
Primary citation | 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. Rigid-body ligand recognition drives cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor triggering J.Biol.Chem., 286:6685-6696, 2011 Cited by 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). PubMed: 21156796DOI: 10.1074/jbc.M110.182394 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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