title: The domains of human fibronectin mediating the binding of alpha antigen, the most immunopotent antigen of mycobacteria that induces protective immunity against mycobacterial infection.
abstract: We have recently shown that alpha antigen (alpha-Ag), the immunodominant antigen of mycobacteria, has a novel fibronectin (FN)-binding motif that is unique among mycobacteria [Naito, Ohara, Matsumoto and Yamada (1998) J. Biol. Chem. 273, 2905-2909]. In this study, we examined the domains of human FN that interacted with alpha-Ag. Fragments of FN generated by either proteolysis or recombinant DNA techniques were compared for their ability to bind to alpha-Ag. Fragments containing either the C-terminal heparin-binding domain or the central cell-binding domain consistently bound to alpha-Ag. The fragment of the C-terminal heparin-binding domain, upon mutation that resulted in the loss of its heparin-binding activity, could not bind with alpha-Ag. These findings suggested that the mutated site, i.e. the main heparin-binding site of FN, was also the principal site for binding to alpha-Ag. The alpha-Ag-binding domains of FN could bind whole mycobacterial bacilli, suggesting that these two domains are important contributors to mycobacterial infection.
authors.affiliation: Department of Oral Bacteriology, Nagasaki University School of Dentistry, Sakamoto 1-7-1, Nagasaki 852-8588, Japan. mnaito@net.nagasaki-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Naito
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
authors.forename: K
authors.initials: K
authors.lastname: Sekiguchi
authors.forename: T
authors.initials: T
authors.lastname: Yamada
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism*; D001667:Binding, Competitive; D019921:Biotinylation; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005780:Gelatin / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D008970:Molecular Weight; D009154:Mutation / Q000235:genetics; D009164:Mycobacterium Infections / Q000276:immunology*; D009163:Mycobacterium bovis / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013820:Thermolysin / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D005353:Fibronectins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C052242:alpha antigens, Mycobacterium; D005780:Gelatin; D006493:Heparin; D013820:Thermolysin