The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand.
The normal function of human intercellular adhesion molecule-1 (ICAM-1) is to provide adhesion between endothelial cells and leukocytes after injury or stress. ICAM-1 binds to leukocyte function-associated antigen (LFA-1) or macrophage-1 antigen (Mac-1). However, ICAM-1 is also used as a receptor by the major group of human rhinoviruses and is a catalyst for the subsequent viral uncoating during cell entry. The three-dimensional atomic structure of the two amino-terminal domains (D1 and D2) of ICAM-1 has been determined to 2.2-A resolution and fitted into a cryoelectron microscopy reconstruction of a rhinovirus-ICAM-1 complex. Rhinovirus attachment is confined to the BC, CD, DE, and FG loops of the amino-terminal Ig-like domain (D1) at the end distal to the cellular membrane. The loops are considerably different in structure to those of human ICAM-2 or murine ICAM-1, which do not bind rhinoviruses. There are extensive charge interactions between ICAM-1 and human rhinoviruses, which are mostly conserved in both major and minor receptor groups of rhinoviruses. The interaction of ICAMs with LFA-1 is known to be mediated by a divalent cation bound to the insertion (I)-domain on the alpha chain of LFA-1 and the carboxyl group of a conserved glutamic acid residue on ICAMs. Domain D1 has been docked with the known structure of the I-domain. The resultant model is consistent with mutational data and provides a structural framework for the adhesion between these molecules.
Bella
J
J
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-1392, USA.
Kolatkar
P R
PR
Marlor
C W
CW
Greve
J M
JM
Rossmann
M G
MG
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011991:Receptors, Virus / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D012229:Rhinovirus / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D011991:Receptors, Virus; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1