Critical threonine and aspartic acid residues within the I domains of beta 2 integrins for interactions with intercellular adhesion molecule 1 (ICAM-1) and C3bi.
Integrins mediate signal transduction through interactions with multiple cellular or extracellular matrix ligands. Evidence is accumulating that the I (or A) domain, a approximately 200-residue inserted sequence in some integrin alpha subunits, mediates ligand binding. We have previously shown that Thr-221 of the putative ligand binding sites within alpha 2 I domain of alpha 2 beta 1 is critical for binding to collagen (Kamata, T., and Takada, Y. (1994) J. Biol. Chem. 269, 26006-26010). Here we report that the mutation of Thr-206 of alpha L blocks intercellular adhesion molecule 1 (ICAM-1) binding to alpha L beta 2 and mutation of Thr-209 of alpha M blocks ICAM-1 and C3bi binding to alpha M beta 2. The data indicate the Thr residues of alpha M and alpha L corresponding to Thr-221 of alpha 2 are critically involved in the ligand interaction with beta 2 integrins. The mutations of the Asp-137 and Asp-239 of alpha L also block ICAM-1 binding to alpha L beta 2, as do the corresponding Asp residues of alpha 2 or alpha M in collagen/alpha 2 beta 1 or C3bi/alpha M beta 2 interactions, respectively. These data suggest that these Thr and Asp residues, conserved among I domains, are critical for interaction with structurally distinct ligands (e.g. ICAMs, C3bi, and collagen).
Kamata
T
T
Department of Vascular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Wright
R
R
Takada
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism; D018821:CD18 Antigens; D016466:CHO Cells; D002448:Cell Adhesion / Q000235:genetics*; D003179:Complement C3b / Q000378:metabolism*; D017124:Conserved Sequence; D006224:Cricetinae; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism; D016177:Macrophage-1 Antigen; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D013912:Threonine / Q000235:genetics / Q000378:metabolism
D018821:CD18 Antigens; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D013912:Threonine; D001224:Aspartic Acid; D003179:Complement C3b