STRUCTURAL BIOLOGY OF IgSF CELL ADHESION MOLECULES. E. Yvonne Jones. Laboratory of Molecular Biophysics, The Rex Richards Building, South Parks Rd., Oxford, OX1 3QU, UK.

Structural studies on cell adhesion molecules, primarily those belonging to the immunoglobulin superfamily (IgSF), will be described. Direct intercellular and cell-matrix interactions are fundamental to the development and maintenance of multicellular organisms. These interactions are mediated by the extracellular regions of specific cell surface receptors, termed cell adhesion molecules. Sequence analysis indicates that the extracellular regions of many of these molecules contain immunoglobulin-like folds, leading to their classification as members of the IgSF. IgSF molecules variously mediate specific adhesion through a broad range interaction modes, homotypic with the same or closely related IgSF molecules, heterotypic with other types of adhesion molecules or even with specific carbohydrates. We have determined the structures of functional portions of several IgSF adhesion molecules by x-ray crystallography. These include representative examples of molecules which function by widely differing adhesion modes; IgSF/IgSF, IgSF/integrin and IgSF/sialylated glycan. The structural adaptations of the basic Ig-like motif which confer the different binding specificities will be assessed.

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Bodian D.L., Jones E.Y., Harlos K., Stuart D.I. and Davis S.J. (1994) Crystal structure of the extracellular region of the human cell adhesion molecule CD2 at 2.5 Å resolution. Structure 2 755-766

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

Vinson M., Van der Merwe P.A., Kelm S., May A., Jones E.Y. and Crocker P.R. (1996) Identification of a putative sialic acid binding site within the amino-terminal immunoglobulin-like domain of sialoadhesin: analysis by site-directed mutagenesis. J. Biol. Chem. (In the press)