1vca: Difference between revisions
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==Overview== | ==Overview== | ||
The cell-surface glycoprotein vascular cell adhesion molecule-1 (VCAM-1; | 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== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bottomley, M | [[Category: Bottomley, M J.]] | ||
[[Category: Clements, J | [[Category: Clements, J M.]] | ||
[[Category: Driscoll, P | [[Category: Driscoll, P C.]] | ||
[[Category: Dudgeon, T | [[Category: Dudgeon, T J.]] | ||
[[Category: Edwards, R | [[Category: Edwards, R M.]] | ||
[[Category: Harlos, K.]] | [[Category: Harlos, K.]] | ||
[[Category: Jones, E | [[Category: Jones, E Y.]] | ||
[[Category: Robinson, R | [[Category: Robinson, R C.]] | ||
[[Category: Stuart, D | [[Category: Stuart, D I.]] | ||
[[Category: immunoglobulin superfamily]] | [[Category: immunoglobulin superfamily]] | ||
[[Category: integrin-binding]] | [[Category: integrin-binding]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:33:45 2008'' | ||
Revision as of 16:33, 21 February 2008
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CRYSTAL STRUCTURE OF AN INTEGRIN-BINDING FRAGMENT OF VASCULAR CELL ADHESION MOLECULE-1 AT 1.8 ANGSTROMS RESOLUTION
OverviewOverview
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.
DiseaseDisease
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 StructureAbout this Structure
1VCA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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