THE COLLAGEN-BINDING DOMAIN OF FIBRONECTIN CONTAINS A HIGH-AFFINITY BINDING-SITE FOR CANDIDA-ALBICANS

A 30-kDa proteolytic fragment from the gelatin/collagen-binding domain of fibronectin is a potent inhibitor of fibronectin binding to Candid a albicans, with a molar inhibition constant equal to that of intact f ibronectin. Recombinant and proteolytic fragments from the cell-, the fibrin I-, and the heparin II-binding domains also inhibit fibronectin binding, but are 13-1000-fold less active. In suspension, binding of fibronectin to C. albicans is regulated by growth conditions and is sp ecific, saturable, time-dependent, reversible, and divalent cation-ind ependent. Scatchard plot analyses indicate the presence of high affini ty (K-d = 1.3 x 10(-9) M) and low affinity (K-d = 1.2 x 10(-7) M) rece ptors. Recombinant or proteolytic fragments from four binding domains of fibronectin promote adhesion of C. albicans. A recombinant fragment corresponding to the cell-binding domain but with the sequence Arg-Gl y-Asp-Ser deleted promotes C. albicans adhesion and inhibits fibronect in binding to C. albicans with the same activity as the natural sequen ce. Furthermore, four peptides containing the Arg-Gly-Asp sequence and the peptides CS-1 and Arg-Glu-Asp-Val did not block the binding of fi bronectin to C. albicans. Thus, in contrast to the specific binding of soluble fibronectin, recognition of immobilized fibronectin by C. alb icans is mediated by several domains of the protein. Interactions with the cell-binding domain are not mediated by the Arg-Gly-Asp or other known recognition sequences as it has been suggested. Binding of fibro nectin also did not correlate with C(3)d binding to the avirulent clon es of C. albicans strain H-12 or with iC(3)b binding to variants of th e strain 4918.