title: Beta 2 (CD18) mutations abolish ligand recognition by I domain integrins LFA-1 (alpha L beta 2, CD11a/CD18) and MAC-1 (alpha M beta 2, CD11b/CD18).
abstract: The "I" domains of the beta 2 (CD18) leukocyte integrins are implicated in ligand binding function. Moreover, rather than recognizing linear peptide sequences, this class of integrins generally recognizes multiple discontinuous sites on immunoglobulin superfamily adhesion receptors. A conserved cluster of oxygenated residues is involved in ligand recognition by beta 1 and beta 3 integrins. In the present study, we evaluated the role of this region in the I domain-containing beta 2 integrins. Recombinant alpha L beta 2 (LFA-1, CD11a/CD18) and alpha M beta 2 (MAC-1, CD11b/CD18) were expressed on COS cells, and function was assessed by adhesion to ICAM-1 or iC3b, respectively. Alanine substitution at position Asp134 or Ser136 in beta 2 produced a complete loss in the capacity of both alpha L beta 2 and alpha M beta 2 to support cell adhesion. In contrast, substitution at Asp128 or Ser138 resulted in loss of beta 2 surface expression when co-transfected with alpha L (CD11a) or alpha M (CD11b). These data provide the first evidence for involvement of the beta 2 subunit in ligand binding to I domain integrins.
authors: Upjohn Laboratories, Kalamazoo, Michigan 49001.
authors: M L
authors: ML
authors: Bajt
authors: T
authors: T
authors: Goodman
authors: S L
authors: SL
authors: McGuire
mesh_terms: D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D012694:Serine / Q000378:metabolism
chemical_list: D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D001224:Aspartic Acid; D012694:Serine