Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 A resolution.

摘要: The cell-surface glycoprotein vascular cell adhesion molecule-1 (VCAM-1; ref. 1) mediates intercellular by specific binding to the integrin very-late antigen-4 (VLA-4, alpha 4 beta 1; 3). VCAM-1, with molecules ICAM-1, ICAM-2, ICAM-3 and mucosal addressin MAd-CAM-1, forms an integrin-binding subgroup of immunoglobulin superfamily. In addition their clinical relevance in inflammation, these act as cellular receptors for viral parasitic agents. predominant form VCAM-1 vivo has amino-terminal extracellular region comprising seven immunoglobulin-like domains. Functional studies have identified a conserved motif domains 1 4, variants which are present N-terminal domain all members superfamily subgroup. We report here crystal structure VLA-4-binding fragment composed first two VCAM-1. (Q38IDSPL) is highly exposed loop between beta-strands C D 1. This exhibits distinctive conformation we predict will be common IgSF molecules. These, additional data, map VLA-4 face CFG beta-sheet, surface previously site adhesive interactions