Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
J Biol Chem. 2012 Apr 13;287(16):12715-22. doi: 10.1074/jbc.M112.339721. Epub 2012 Feb 24.
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.
牙周炎是人类最常见的微生物病因疾病。牙周病原体的生存依赖于逃避补体介导的破坏。牙龈卟啉单胞菌是牙周炎的重要致病因子，通过将补体因子 H（FH）结合到其表面来逃避替代补体级联的杀伤。结合的 FH 被牙龈卟啉单胞菌蛋白酶、齿龈蛋白酶迅速切割。在本报告中，解决了 1.7Å 分辨率的牙龈卟啉单胞菌 FH 结合蛋白 FhbB 的结构。FhbB 具有独特的折叠结构，赋予其高热稳定性。使用表面等离子体共振评估了 FH/FhbB 相互作用的动力学。证明了在微摩尔范围内（低亲和力）的 K(D) 值，并观察到快速的离速动力学。定点突变和蔗糖八硫酸竞争测定的综合结果表明，FhbB 的带负电荷的表面在 FH 补体控制蛋白模块 7 内结合。这项研究为 FH/FhbB 相互作用的分子基础提供了重要的新见解，并加深了我们对牙龈卟啉单胞菌在牙周病发展和进展中所起作用的理解。
