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) do main, a similar to 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),