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

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

Research output: Contribution to journalArticle

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Abstract

THE cell-surface glycoprotein vascular cell adhesion molecule-1 (VCAM-1; ref. 1) mediates intercellular adhesion2 by specific binding to the integrin very-late antigen-4 (VLA-4, α4β1; 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 immuno-globulin superfamily. In addition to their clinical relevance in inflammation, these molecules act as cellular receptors for viral and parasitic agents2. The predominant form of VCAM-1 in vivo has an ammo-terminal extracellular region comprising seven immunoglobulin-like domains. Functional studies4-7 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 β-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 β-sheet, the surface previously identified8 as the site for intercellular adhesive interactions between members of the immunoglobulin superfamily.

Original languageEnglish
Pages (from-to)539-544
Number of pages6
JournalNature
Volume373
Issue number6514
DOIs
Publication statusPublished - Feb 9 1995
Externally publishedYes

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Vascular Cell Adhesion Molecule-1
Integrin alpha4beta1
Integrins
Intercellular Adhesion Molecule-1
Immunoglobulins
Membrane Glycoproteins
Globulins
Adhesives
Inflammation

ASJC Scopus subject areas

  • General

Cite this

Jones, E. Y., Harlos, K., Bottomley, M. J., Robinson, R. C., Driscoll, P. C., Edwards, R. M., ... Stuart, D. I. (1995). Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 Å resolution. Nature, 373(6514), 539-544. https://doi.org/10.1038/373539a0

Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 Å resolution. / 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.

In: Nature, Vol. 373, No. 6514, 09.02.1995, p. 539-544.

Research output: Contribution to journalArticle

Jones, EY, Harlos, K, Bottomley, MJ, Robinson, RC, Driscoll, PC, Edwards, RM, Clements, JM, Dudgeon, TJ & Stuart, DI 1995, 'Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule-1 at 1.8 Å resolution', Nature, vol. 373, no. 6514, pp. 539-544. https://doi.org/10.1038/373539a0
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 Å resolution. In: Nature. 1995 ; Vol. 373, No. 6514. pp. 539-544.
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