1VCA

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

Summary for 1VCA

• Entry DOI: 10.2210/pdb1vca/pdb
• Descriptor: HUMAN VASCULAR CELL ADHESION MOLECULE-1 (2 entities in total)
• Functional Keywords: immunoglobulin superfamily, integrin-binding, cell adhesion protein
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P19320
• Total number of polymer chains: 2
• Total formula weight: 45071.15

Authors

Jones, E.Y.,Harlos, K.,Bottomley, M.J.,Robinson, R.C.,Driscoll, P.C.,Edwards, R.M.,Clements, J.M.,Dudgeon, T.J.,Stuart, D.I. (deposition date: 1995-03-21, release date: 1995-09-15, Last modification date: 2024-10-30)

Primary citation

Jones, E.Y.,Harlos, K.,Bottomley, M.J.,Robinson, R.C.,Driscoll, P.C.,Edwards, R.M.,Clements, J.M.,Dudgeon, T.J.,Stuart, D.I.
Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 A resolution.
Nature, 373:539-544, 1995

PubMed Abstract: 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.

PubMed: 7531291
DOI: 10.1038/373539a0

Experimental method

X-RAY DIFFRACTION (1.8 Å)