title: Hemoglobin-induced binding of Candida albicans to the cell-binding domain of fibronectin is independent of the Arg-Gly-Asp sequence.
abstract: Hemoglobin specifically induces fibronectin (FN) binding to the pathogenic yeast Candida albicans. When grown in the complex medium Sabouraud broth, C. albicans expresses receptors that bind to several domains of FN. Growth in defined medium supplemented with 0.1% hemoglobin, however, enhanced the binding of FN to a single class of receptors, with a Kd = 4.6 x 10(-8) M. Competitive binding assays using recombinant and proteolytic fragments of FN revealed that the cell-binding domain mediated this interaction. A recombinant 40-kDa fragment of FN consisting of type III repeats 9 to 13 had an inhibitory activity similar to that of the entire 120-kDa cell-binding domain, indicating that the C-terminal portion of the cell-binding domain contains the binding site. A recombinant 33-kDa fragment of the cell-binding domain and a 33-kDa fragment with the RGD sequence deleted had the same inhibitory activities, demonstrating that the RGD sequence recognized by some mammalian integrins is not required. The addition of hemoglobin to the culture medium also enhanced Candida cell adhesion to immobilized FN and to 120- and 40-kDa fragments of FN but not to the collagen-binding or fibrin I domains. Using ligand protection, we identified a surface protein from C. albicans with an apparent molecular mass of 55 kDa that was protected by both FN and the 40-kDa fragment derived from the cell-binding domain. Therefore, hemoglobin both induces FN binding and changes the relative affinities of C. albicans for the cell- and collagen-binding domains of FN.
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1500, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yan
authors.forename: R G
authors.initials: RG
authors.lastname: Rodrigues
authors.forename: D D
authors.initials: DD
authors.lastname: Roberts
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002176:Candida albicans / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology*; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: D005353:Fibronectins; D006454:Hemoglobins; D009842:Oligopeptides; D010446:Peptide Fragments; C047981:arginyl-glycyl-aspartic acid