3OSK

Crystal structure of human CTLA-4 apo homodimer

3OSK の概要

• エントリーDOI: 10.2210/pdb3osk/pdb
• 分子名称: Cytotoxic T-lymphocyte protein 4, 2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: beta sandwich, homodimer, immunoglobulin superfamily (beta sandwich) fold, receptor, signalling, b7-1(cd80), b7-2(cd86), membrane, immune system
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P16410
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28580.48

構造登録者

Yu, C.,Sonnen, A.F.-P.,Ikemizu, S.,Stuart, D.I.,Gilbert, R.J.C.,Davis, S.J. (登録日: 2010-09-09, 公開日: 2010-12-08, 最終更新日: 2024-10-30)

主引用文献

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

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: 21156796
DOI: 10.1074/jbc.M110.182394

実験手法

X-RAY DIFFRACTION (1.8 Å)