The cell adhesion domain in plasma vitronectin is cryptic.
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
D
D
Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA. seiffeda@a1.lldmpc.umc.dupont.com
Smith
J W
JW
D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011487:Protein Conformation; D011489:Protein Denaturation; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism; D019096:Vitronectin / Q000097:blood* / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D009842:Oligopeptides; D017395:Plasminogen Activator Inhibitor 1; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D019030:Receptors, Vitronectin; D019096:Vitronectin; C051382:arginyl-glycyl-aspartic acid directed cell adhesion receptor; C047981:arginyl-glycyl-aspartic acid