DISTINCT STRUCTURAL REQUIREMENTS FOR INTERACTION OF THE INTEGRINS ALPHA-5-BETA-1, ALPHA-NU-BETA-5, AND ALPHA-NU-BETA-6 WITH THE CENTRAL CELL-BINDING DOMAIN IN FIBRONECTIN

At least 10 different members of the integrin family have been reporte d to bind to fibronectin, and eight of these interact with the arginin e-glycine-aspartic acid (RGD) site in the tenth type III repeat. Howev er, studies utilizing recombinant fibronectin fragments have shown tha t for three of these, alpha 5 beta 1, alpha IIb beta 3, and alpha v be ta 3, the structural requirements for binding to fibronectin differ. I n the present study, we report that two additional integrins, alpha v beta 6, and alpha v beta 5 also demonstrate unique requirements for in teraction with recombinant fibronectin fragments. alpha v beta 6, like alpha v beta 3, can support cell adhesion to the RGD-containing tenth repeat alone, and does not require the presence of a synergy site in the adjacent ninth repeat. In the cells used in this study, alpha v be ta 5 only minimally supported adhesion to intact fibronectin, but did support adhesion to fragments composed of the eighth, ninth and tenth repeats or the tenth repeat, alone. Mutant fragments in which the eigh th and tenth repeals were adjacent to one another enhanced adhesion me diated by alpha v beta 5, as well as adhesion mediated by alpha v beta 6. alpha v beta 5 and alpha v beta 6-mediated adhesion to all fibrone ctin fragments required interaction with the RGD site, as inferred by inhibition of adhesion with an RGD-containing peptide. These data sugg est that each integrin that interacts with the RGD site in fibronectin has unique structural requirements for this interaction.