Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 Å resolution View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1995-02

AUTHORS

E Y Jones, K Harlos, M J Bottomley, R C Robinson, P C Driscoll, R M Edwards, J M Clements, T J Dudgeon, D I Stuart

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. More... »

PAGES

539-544

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/373539a0

DOI

http://dx.doi.org/10.1038/373539a0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051713115

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/7531291


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