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Vitronectin (Vn) is a major adhesive glycoprotein in blood. However, many of the functions of Vn are regulated by its conformational state and degree of multimerization. Here, the ability of native and denatured Vn to bind to integrin adhesion receptors was compared. Three lines of evidence suggest that the native, plasma form of Vn is not an adhesive glycoprotein. (i) Antibodies that bind in close proximity to the cell adhesion domain of Vn fail to bind to native Vn present in unfractionated plasma. (ii) Denatured Vn binds to both glycoprotein IIb/IIIa and alphavbeta3 in a dose-dependent manner. In contrast, native Vn is unable to bind either integrin. (iii) Thermal denaturation of native Vn, or its complexation with type 1 plasminogen activator inhibitor, exposed the cell adhesion domain of Vn. Thus, while plasma Vn is unable to bind integrins and is not an adhesive glycoprotein, the conformationally altered from of the protein binds avidly to both alphavbeta3 and glycoprotein IIb/IIIa. The data presented here indicate that such conformational changes in Vn are likely to occur in areas of tissue injury and thrombosis.
Seiffert et al. (Thu,) studied this question.