THE CELL-ADHESION DOMAIN IN PLASMA VITRONECTIN IS CRYPTIC

Vitronectin (Vn) is a major adhesive glycoprotein in blood. However, m any of the functions of Vn are regulated by its conformational state a nd degree of multimerization. Here, the ability of native and denature d Vn to bind to integrin adhesion receptors was compared. Three lines of evidence suggest that the native, plasma form of Vn is not an adhes ive glycoprotein. (i) Antibodies that bind in close proximity to the c ell adhesion domain of Vn fail to bind to native Vn present in unfract ionated plasma. (ii) Denatured Vn binds to both glycoprotein IIb/IIIa and alpha(v) beta(3), in a dose-dependent manner. In contrast, native Vn is unable to bind either integrin. (iii) Thermal denaturation of na tive Vn, or its complexation with type 1 plasminogen activator inhibit or, exposed the cell adhesion domain of Vn. Thus, while plasma Vn is u nable to bind integrins and is not an adhesive glycoprotein, the confo rmationally altered from of the protein binds avidly to both alpha(v) beta(3), and glycoprotein IIb/IIIa. The data presented here indicate t hat such conformational changes in Vn are likely to occur in areas of tissue injury and thrombosis.