LIGAND-INDUCED CONFORMATIONAL CHANGE WITHIN THE CD2 ECTODOMAIN ACCOMPANIES RECEPTOR CLUSTERING - IMPLICATION FOR MOLECULAR LATTICE FORMATION

Citation
J. Li et al., LIGAND-INDUCED CONFORMATIONAL CHANGE WITHIN THE CD2 ECTODOMAIN ACCOMPANIES RECEPTOR CLUSTERING - IMPLICATION FOR MOLECULAR LATTICE FORMATION, Journal of Molecular Biology, 263(2), 1996, pp. 209-226
Citations number
86
Categorie Soggetti
Biology
ISSN journal
00222836
Volume
263
Issue
2
Year of publication
1996
Pages
209 - 226
Database
ISI
SICI code
0022-2836(1996)263:2<209:LCCWTC>2.0.ZU;2-Y
Abstract
CD2 mediates interaction between T cells and their cognate partners th rough its CD58-binding membrane-distal adhesion domain (D1) facilitati ng T cell receptor (TCR) triggering. A neoepitope defined by anti-CD2R monoclonal antibodies (mAbs) has suggested structural alteration with in the CD2 ectodomain during T cell activation. Here, we map CD2R to t he flexible CD2 linker region between D1 and the membrane-proximal ext racellular domain (D2) and show that exposure of this conformational s ite is independent of temperature and metabolic energy. Co-ligation of CD2 and CD58 molecules on opposing cells within a conjugate pair indu ces CD2R and redistributes CD2 to the region of cell-cell contact. The se CD2R(+) molecules, in contrast to the CD2R(-) molecules, are tightl y clustered on the T cell surface. Hence, a ligand-mediated increase i n the D1-D2 interdomain angle apparently exposes CD2R, facilitates pac king of CD2 molecules in a clustered array and is linked to CD2-mediat ed adhesion and activation events. Conformational alteration of this t ype may be generally important in ordered lattice formation involving surface receptors. (C) 1996 Academic Press Limited