title: Structure of factor H-binding protein B (FhbB) of the periopathogen, Treponema denticola: insights into progression of periodontal disease.
abstract: Periodontitis is the most common disease of microbial etiology in humans. Periopathogen survival is dependent upon evasion of complement-mediated destruction. Treponema denticola, an important contributor to periodontitis, evades killing by the alternative complement cascade by binding factor H (FH) to its surface. Bound FH is rapidly cleaved by the T. denticola protease, dentilisin. In this report, the structure of the T. denticola FH-binding protein, FhbB, was solved to 1.7 Å resolution. FhbB possesses a unique fold that imparts high thermostability. The kinetics of the FH/FhbB interaction were assessed using surface plasmon resonance. A K(D) value in the micromolar range (low affinity) was demonstrated, and rapid off kinetics were observed. Site-directed mutagenesis and sucrose octasulfate competition assays collectively indicate that the negatively charged face of FhbB binds within FH complement control protein module 7. This study provides significant new insight into the molecular basis of FH/FhbB interaction and advances our understanding of the role that T. denticola plays in the development and progression of periodontal disease.
authors.affiliation: Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Miller
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Bell
authors.forename: John V
authors.initials: JV
authors.lastname: McDowell
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Conrad
authors.forename: John W
authors.initials: JW
authors.lastname: Burgner
authors.forename: Annie
authors.initials: A
authors.lastname: Héroux
authors.forename: Richard T
authors.initials: RT
authors.lastname: Marconi
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D017242:Complement Factor H / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D018450:Disease Progression; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010510:Periodontal Diseases / Q000382:microbiology*; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance; D048373:Treponema denticola / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D006025:Glycosaminoglycans; D017242:Complement Factor H