1vca

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spinqualitylabelsall models 1vca, resolution 1.8Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF AN INTEGRIN-BINDING FRAGMENT OF VASCULAR CELL ADHESION MOLECULE-1 AT 1.8 ANGSTROMS RESOLUTION

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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

Disease

Known diseases associated with this structure: CRASH syndrome OMIM:[308840], Corpus callosum, partial agenesis of OMIM:[308840], Hydrocephalus due to aqueductal stenosis OMIM:[308840], Hydrocephalus with Hirschsprung disease and cleft palate OMIM:[308840], Hydrocephalus with congenital idiopathic intestinal pseudoobstruction OMIM:[308840], MASA syndrome OMIM:[308840]

About this Structure

1VCA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 A resolution., Jones EY, Harlos K, Bottomley MJ, Robinson RC, Driscoll PC, Edwards RM, Clements JM, Dudgeon TJ, Stuart DI, Nature. 1995 Feb 9;373(6514):539-44. PMID:7531291

Page seeded by OCA on Fri Feb 15 17:04:38 2008