EVIDENCE THAT THE INTEGRIN BETA-3 AND BETA-5 SUBUNITS CONTAIN A METALION-DEPENDENT ADHESION SITE-LIKE MOTIF BUT LACK AN I-DOMAIN

The amino-terminal domain of each integrin beta subunit is hypothesize d to contain an ion binding site that is key to cell adhesion, A new h ypothesis regarding the structure of this site is suggested by the cry stallization of the I domains of the integrin alpha(L) and alpha(M) su bunits (Lee, J.-O., Rieu, P., Arnaout, M. A., and Liddington, R. (1995 ) Cell 80, 631-638; Qu, A., and Leahy, D. J. (1995) Proc. Natl, Acad, Sci, U.S.A. 92, 10277-10281), In those proteins, an essential metal io n is bound by a metal ion-dependent adhesion site (MIDAS), The MIDAS i s presented at the apex of a larger protein module called an I domain, The metal ligands in the MIDAS can be separated into three distantly spaced clusters of oxygenated residues, These three coordination sites also appear to exist in the integrin beta 3 and beta 5 subunits, Here , we examined the putative metal binding site within beta 3 and beta 5 using site-directed mutagenesis and ligand binding studies, We also i nvestigated the fold of the domain containing the putative metal bindi ng site using the PHD structural algorithm. The results of the study p oint to the similarity between the integrin beta subunits and the MIDA S motif at two of three key coordination points, Importantly though, t he study failed to identify a residue in either beta subunit that corr esponds to the second metal coordination group in the MIDAS, Moreover, structural algorithms indicate that the fold of the beta subunits is considerably different than the I domains, Thus, the integrin beta sub units appear to present a MIDAS-like motif in the context of a protein module that is structurally distinct from known I domains.