A DIMERIC CRYSTAL-STRUCTURE FOR THE N-TERMINAL 2 DOMAINS OF INTERCELLULAR-ADHESION-MOLECULE-1

The 3.0-Angstrom structure of a 190-residue fragment of intercellular adhesion molecule-1 (ICAM-1, CD54) reveals two tandem Ig-superfamily ( IgSF) domains. Each of two independent molecules dimerizes identically with a symmetry-related molecule over a hydrophobic interface on the BED sheet of domain 1, in agreement with dimerization of ICAM-1 on the cell surface. The residues that bind to the integrin LFA-1 are well o riented for bivalent binding in the dimer, with the critical Glu-34 re sidues pointing away from each other on the periphery. Residues that b ind to rhinovirus are in the flexible BC and FG loops at the tip of do main 1, and these and the upper half of domain 1 are web exposed in th e dimer for docking to virus. By contrast, a residue important for bin ding to Plasmodium falciparum-infected erythrocytes is in the dimer in terface. The presence of A' strands in both domains 1 and 2, conserved hydrogen bonds at domain junctions, and elaborate hydrogen bond netwo rks around the key integrin binding residues in domain 1 make these do mains suited to resist tensile forces during adhesive interactions. A subdivision of the intermediate (I) set of IgSF domains is proposed in which domain 1 of ICAM-1 and previously described I set domains belon g to the I1 set and domain 2 of ICAM-1, ICAM-2, and vascular cell adhe sion molecule-1 belong to the I2 set.