title: The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus.
abstract: Intercellular adhesion molecule 1 (ICAM-1, CD54) binds to the integrin LFA-1 (CD11a/CD18), promoting cell adhesion in immune and inflammatory reactions. ICAM-1 is also subverted as a receptor by the major group of rhinoviruses. Electron micrographs show that ICAM-1 is a bent rod, 18.7 nm long, suggesting a model in which the five immunoglobulin-like domains are oriented head to tail at a small angle to the rod axis. ICAM-1 sequences important to binding LFA-1, rhinovirus, and four monoclonal antibodies were identified through the characterization of chimeric ICAM-1 molecules and mutants. The amino-terminal two immunoglobulin-like domains of ICAM-1 appear to interact conformationally. Domain 1 of ICAM-1 contains the primary site of contact for both LFA-1 and rhinovirus; the presence of domains 3-5 markedly affects the accessibility of the binding site for rhinovirus and less so for LFA-1. The binding sites appear to be distinct but overlapping; rhinovirus binding also differs from LFA-1 binding in its lack of divalent cation dependence. Our analysis suggests that rhinoviruses mimic LFA-1 in binding to the most membrane-distal, and thus most accessible, site of ICAM-1.
authors.affiliation: Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: D E
authors.initials: DE
authors.lastname: Staunton
authors.forename: M L
authors.initials: ML
authors.lastname: Dustin
authors.forename: H P
authors.initials: HP
authors.lastname: Erickson
authors.forename: T A
authors.initials: TA
authors.lastname: Springer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002678:Chimera; D002872:Chromosome Deletion; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1; D007700:Kinetics; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D011485:Protein Binding; D011487:Protein Conformation; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*; D011991:Receptors, Virus / Q000235:genetics*; D012229:Rhinovirus / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D015345:Oligonucleotide Probes; D016028:Receptors, Leukocyte-Adhesion; D011991:Receptors, Virus; D018799:Intercellular Adhesion Molecule-1