Many integrin adhesion receptors bind ligands containing the Arg-Gly-Asp (RGD) peptide motif. Most integrins exhibit considerable specificity for particular ligands and can distinguish among the many conformations of RGD. In this study we identify the domain of the integrin ␤ subunit involved in determining ligand binding specificity. Chimeras of ␤3 and ␤5, the most homologous integrin ␤ subunits, were expressed with ␣v on the surface of human 293 cells. The ligand binding phenotype of each

more »

... era was assessed using the ligands Fab-9 and fibrinogen, both of which have a binding preference for ␣v␤3. The results of the study show that when exons C and D of the ␤3 subunit (residues 95-233) are substituted into ␤5, the chimera gained the ability to bind Fab-9 with an affinity close to that of wild-type ␣v␤3. This chimera was able to mediate cell adhesion to fibrinogen. Furthermore, the swap of only a 39-residue segment of this larger domain, ␤3 residues 164 -202, into the backbone of ␤5 enabled the chimeric integrin to bind soluble Fab-9. This small domain is highly divergent among the integrin ␤ subunits, suggesting that it may play a role in determining ligand selection by all integrins.