title: Contribution of N-linked glycans to the conformation and function of intercellular adhesion molecules (ICAMs).
abstract: The crystal structures of the glycosylated N-terminal two domains of ICAM-1 and ICAM-2 provided a framework for understanding the role of glycosylation in the structure and function of intercellular adhesion molecules (ICAMs). The most conserved glycans were less flexible in the structures, interacting with protein residues and contributing to receptor folding and expression. The first N-linked glycan in ICAM-2 contacts an exposed tryptophan residue, defining a conserved glycan-W motif critical for the conformation of the integrin binding domain. The absence of this motif in human ICAM-1 exposes regions used in receptor dimerization and rhinovirus recognition. Experiments with soluble molecules having the N-terminal two domains of human ICAMs identified glycans of the high mannose type N-linked to the second domain of the dendritic cell-specific ICAM-grabbing nonintegrin lectin-ligands ICAM-2 and ICAM-3. About 40% of those receptor molecules bear endoglycosidase H sensitive glycans responsible of the lectin binding activity. High mannose glycans were absent in ICAM-1, which did not bind to the lectin, but they appeared in ICAM-1 mutants with additional N-linked glycosylation and lectin binding activity. N-Linked glycosylation regulate both conformation and immune related functions of ICAM receptors.
authors.affiliation: Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Científicas, Campus Universidad Autonoma, 28049 Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Jiménez
authors.forename: Pedro
authors.initials: P
authors.lastname: Roda-Navarro
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Springer
authors.forename: José M
authors.initials: JM
authors.lastname: Casasnovas
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011134:Polysaccharides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism; D013329:Structure-Activity Relationship; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1; D037102:Lectins; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C065289:ICAM2 protein, human