The structure of the two amino-terminal domains of human intercellular adhesion molecule-1 suggests how it functions as a rhinovirus receptor

The normal function of human intercellular adhesion molecule-1 (ICAM-1) is to provide adhesion between endothelial cells and leukocytes after injury o r stress. ICAM-1 binds to leukocyte function-associated antigen (LFA-I) or macrophage-l antigen (Mac-1). However, ICAM-1 is also utilized as a recepto r by the major group of human rhinoviruses and is a catalyst for the subseq uent viral uncoating during cell entry. The three-dimensional atomic struct ure of the two amino-terminal domains (D1 and D2) of ICAM-1 has been determ ined to 2.2 Angstrom resolution and fitted into a cryo-electron microscopy reconstruction of a rhinovirus-ICAM-1 complex. Rhinovirus attachment is con fined to the BC, CD, DE and FG loops of the amino-terminal immunoglobulin-l ike domain (D1) at the end distal to the cellular membrane. The loops are c onsiderably different in structure to those of human ICAM-2 or murine ICAM- 1 which do not bind rhinoviruses. There are extensive charge interactions b etween ICAM-1 and human rhinoviruses, which are mostly conserved in both ma jor and minor receptor groups of rhinoviruses. The interaction of ICAMs wit h LFA-I is known to be mediated by a divalent cation bound to the I-(insert ion) domain on the cc chain of LFA-I and the carboxy group of a conserved g lutamic acid residue on ICAMs. Domain D1 has been docked with the known str ucture of the I-domain. The resultant model is consistent with mutational d ata and provides a structural framework for the adhesion between these mole cules. (C) 1999 Elsevier Science B.V. All rights reserved.