Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 A resolution
| Autor: | Paul C. Driscoll, M. J. Bottomley, John M. Clements, R M Edwards, David I. Stuart, Robert Robinson, Karl Harlos, E Y Jones, T. J. Dudgeon |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Protein Conformation
Integrin Molecular Sequence Data CD2 Antigens Vascular Cell Adhesion Molecule-1 Crystallography X-Ray Protein Structure Secondary Protein structure Receptors Very Late Antigen Addressin Computer Graphics Escherichia coli Humans Amino Acid Sequence Binding site Cell adhesion Integrin binding Multidisciplinary Binding Sites biology Sequence Homology Amino Acid Cell adhesion molecule Recombinant Proteins Cell biology Biochemistry Mutagenesis biology.protein Immunoglobulin superfamily Cell Adhesion Molecules |
| Zdroj: | Scopus-Elsevier |
| DOI: | 10.1038/373539a0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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