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)

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 cons...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-01, Vol.270 (1), p.94-98
Main Authors: Bajt, M L, Goodman, T, McGuire, S L
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Aspartic Acid - metabolism
Cells, Cultured
Humans
Integrins - genetics
Integrins - metabolism
Lymphocyte Function-Associated Antigen-1 - genetics
Lymphocyte Function-Associated Antigen-1 - metabolism
Macrophage-1 Antigen - genetics
Macrophage-1 Antigen - metabolism
Molecular Sequence Data
Mutation
Sequence Alignment
Serine - metabolism
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Summary: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.
ISSN:0021-9258