Critical residues for ligand binding in an I domain-like structure of the integrin beta1 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 profiles and the homology of sequences between the alpha and beta subunits. This study was designed to determine whether the region of the beta1 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 addition to the previously reported Asp-130) using site-directed mutagenesis. The critical residues for ligand binding are located in several of loop structures of the region (or in a potential loop between an alpha helix and a beta strand), which have been predicted using multiple secondary 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.