CRYSTALS STRUCTURE OF ICAM-2 REVEALS A DISTINCTIVE INTEGRIN RECOGNITION SURFACE

Recognition by integrin proteins on the cell surface regulates the adh esive interactions between cells and their surroundings(1,2). The stru cture of the 'I' domain that is found in some but not all integrins, h as been determined(3,4). However, the only integrin ligands for which structures are known, namely fibronectin and VCAM-1 (refs 5-7), are re cognized by integrins that lack I domains. The intercellular adhesion molecules ICAM-1, 2 and 3 are, like VCAM-1, members of the immunoglobu lin superfamily (IgSF), but they are recognized by an I domain-contain ing integrin, lymphocyte-function-associated antigen 1 (LFA-1, or CD11 a/CD18). Here we present the crystal structure of the extracellular re gion of ICAM-2. The glutamic acid residue at position 37 is critical f or LFA-1 binding and is proposed to coordinate the Mg2+ ion in the I d omain; this Glu 37 is surrounded by a relatively flat recognition surf ace and lies in a beta-strand, whereas the critical aspartic acid resi due in VCAM-1 and fibronectin lie in protruding loops. This finding su ggests that there are differences in the architecture of recognition s ites between integrins that contain or lack I domains. A bend between domains 1 and 2 of ICAM-2 and a tripod-like arrangement of N-linked gl ycans in the membrane-proximal region of domain 2 may be important for presenting the recognition surface to LFA-1. A model of ICAM-1 based on the ICAM-2 structure provides a framework for understanding its rec ognition by pathogens.