Integrins mediate signal transduction through interactions with multiple cellular or extracellular matrix ligands. Evidence is accumulating that the I (or A) domain, a ~200-residue inserted sequence in some integrin α subunits, mediates ligand binding. We have previously shown that Thr-221 of the putative ligand binding sites within α2 I domain of α2β1 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 αL blocks intercellular adhesion molecule 1 (ICAM-1) binding to αLβ2 and mutation of Thr-209 of αM blocks ICAM-1 and C3bi binding to αMβ2. The data indicate the Thr residues of αM and aL corresponding to Thr-221 of α2 are critically involved in the ligand interaction with β2 integrins. The mutations of the Asp-137 and Asp-239 of αL also block ICAM-1 binding to αLβ2, as do the corresponding Asp residues of α2 or αM in collagen/α2β1 or C3bi/αMβ2 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).
ASJC Scopus subject areas