D. Seiffert, THE GLYCOSAMINOGLYCAN BINDING-SITE GOVERNS LIGAND-BINDING TO THE SOMATOMEDIN-B DOMAIN OF VITRONECTIN, The Journal of biological chemistry, 272(15), 1997, pp. 9971-9978
The ligand binding functions of vitronectin (Vn) are regulated by its
conformational state/degree of multimerization. In the native plasma f
orm of Vn, the C-terminal glycosaminoglycan (GAG) binding domain is be
lieved to be cryptic. Here, evidence is provided that the addition of
fucoidan or dextran sulfate to unfractionated plasma results in the fo
rmation of covalently and non-covalently stabilized Vn multimers. Thes
e multimers express conformationally sensitive antibody epitopes and l
igand binding sites located in the N terminus of the Vn molecule. Whil
e heparin forms complexes with monomeric plasma Vn and induces conform
ational changes, a reduction in ionic strength is required for inducti
on of multimerization. In addition, heparin serves as a template for t
he assembly of type 1 plasminogen activator inhibitor induced disulfid
e-linked Vn multimers. These results support a new model for the struc
ture of native Vn. The C-terminal GAG binding domain is predicted to b
e exposed in the native conformation, whereas the N terminus is crypti
c. Ligand binding to the GAG binding site unfolds the N terminus, ther
eby exposing cryptic ligand binding sites.