CRITICAL RESIDUES FOR LIGAND-BINDING IN AN I-DOMAIN-LIKE STRUCTURE OFTHE INTEGRIN BETA-1 SUBUNIT

Several integrin alpha subunits have an inserted sequence of about 200 residues (the I or A domain) that is critical for ligand interactions . The presence of an I domain-like structure within the integrin beta subunit has been proposed based on the similarity of the hydropathy pr ofiles and the homology of sequences between the alpha and beta subuni ts. This study was designed to determine whether the region of the bet a 1 subunit that includes residues 101-335 has the characteristics of an I domain. We found novel critical residues for ligand binding (Ser- 132, Asn-224, Asp-226, Glu-229, Asp-233, Asp-267, and Asp-295, in addi tion to the previously reported Asp-130) using site-directed mutagenes is, The critical residues for ligand binding are located in several of loop structures of the region (or in a potential loop between an alph a helix and a beta strand), which have been predicted using multiple s econdary structure prediction methods. The data suggest that the beta subunit has multiple disrupted critical oxygenated residues for ligand binding similar to those found in the alpha I domain.