title: The tandem beta-zipper model defines high affinity fibronectin-binding repeats within Staphylococcus aureus FnBPA.
abstract: Binding of the fibronectin-binding protein FnBPA from Staphylococcus aureus to the human protein fibronectin has previously been implicated in the development of infective endocarditis, specifically in the processes of platelet activation and invasion of the endothelium. We recently proposed a model for binding of fibronectin to FnBPA in which the bacterial protein contains 11 potential binding sites (FnBPA-1 to FnBPA-11), each composed of motifs that bind to consecutive fibronectin type 1 modules in the N-terminal domain of fibronectin. Here we show that six of the 11 sites bind with dissociation constants in the nanomolar range; other sites bind more weakly. The high affinity binding sites include FnBPA-1, the sequence of which had previously been thought to be encompassed by the fibrinogen-binding A domain of FnBPA. Both the number and sequence conservation of the type-1 module binding motifs appears to be important for high affinity binding. The in vivo relevance of the in vitro binding studies is confirmed by the presence of antibodies in patients with S. aureus infections that specifically recognize complexes of these six high affinity repeats with fibronectin.
authors.affiliation: Department of Biology, University of York, P.O. Box 373, York YO10 5YW, United Kingdom.
authors.forename: Nicola A G
authors.initials: NA
authors.lastname: Meenan
authors.forename: Livia
authors.initials: L
authors.lastname: Visai
authors.forename: Viviana
authors.initials: V
authors.lastname: Valtulina
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schwarz-Linek
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Norris
authors.forename: Sivashankarappa
authors.initials: S
authors.lastname: Gurusiddappa
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
authors.forename: Pietro
authors.initials: P
authors.lastname: Speziale
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Potts
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000276:immunology; D020816:Amino Acid Motifs / Q000276:immunology; D000907:Antibodies, Bacterial / Q000276:immunology; D001422:Bacterial Adhesion / Q000276:immunology; D004697:Endocarditis, Bacterial / Q000276:immunology / Q000382:microbiology; D004730:Endothelium, Vascular / Q000276:immunology / Q000382:microbiology; D005353:Fibronectins / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D015539:Platelet Activation / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D005353:Fibronectins; C078635:fibronectin-binding proteins, bacterial