Role of Clp proteins in pathophysiology of Streptococcus mutans

摘要 变形链球菌已强烈暗示为人类的主要病原体 龋病它也是感染性心内膜炎的重要病原体。S.变形菌在口腔内定植 通过在牙齿表面形成多样的、多物种的生物膜， 斑块S.变形菌通过有效地响应口腔的恶劣环境而存活 各种环境通量，包括严重的营养限制，pH值的波动， 温度将细菌暴露于这些不利环境中可以诱导应激耐受性 通过表达多种蛋白质来提供交叉保护， 环境挑战。酪蛋白分解蛋白酶（Clp）家族蛋白质，其包含 HSP 100/Clp分子伴侣和ClpP蛋白酶，构成了细菌蛋白质质量的核心 控制系统参与热和其他压力反应。ClpP，一种小的细胞质丝氨酸 蛋白酶，与伴侣ATP酶伴侣结合形成功能复合物， 特异性靶向受损或错误折叠的蛋白质进行降解（统称为 调节蛋白水解）。当ClpP降解受损的蛋白质时，ATP酶 组分决定底物特异性。与其他厚壁菌门一样，链球菌编码5个 Clp ATP酶，其中只有三种（ClpC，ClpE和ClpX）与ClpP相互作用形成活性 配合物ClpP是胁迫耐受性所需的主要细胞内蛋白酶 反应，细菌素的产生和生物膜的形成等，而ClpX/P是主要的 我们最近发现ClpE/P也参与蛋白质的质量控制， 链球菌。然而，底物识别和降解的分子机制， ClpX/P和ClpE/P在这些生物体中还没有很好的理解。事实上，我们对 蛋白质质量控制及其在链球菌毒力中的作用。我们的长期目标是 了解调节蛋白水解的分子机制在S。变形菌和其他口腔 链球菌。

ABSTRACT Streptococcus mutans has been strongly implicated as the principal etiological agent in human dental caries. It is also an important agent of infective endocarditis. S. mutans colonizes the oral cavity through the formation of diverse, multispecies biofilms on the tooth surface, known as dental plaque. S. mutans flourishes in the hostile environment of the oral cavity by responding efficiently to various environmental fluxes, including severe nutrient limitation, fluctuations in pH and temperature. Exposure of bacteria to these adverse environments can induce a stress tolerance response through expression of a wide variety of proteins that provide cross-protection against environmental challenges. The caseinolytic protease (Clp) family proteins, which contain HSP100/Clp chaperones and the ClpP protease, constitute the core of bacterial protein quality control systems involved in thermal and other stress responses. ClpP, a small cytoplasmic serine protease, associates with a partner ATPase chaperone to form a functional complex that specifically targets damaged or mis-folded proteins for degradation (collectively known as regulated proteolysis) during stresses. While ClpP degrades the damaged protein, the ATPase component determines the substrate specificity. Like other Firmicutes, streptococci encode five Clp ATPases and only three of these (ClpC, ClpE, and ClpX) interact with ClpP to form active complexes. ClpP is the primary intracellular protease that is required for stress tolerance response, bacteriocin production, and biofilm formation among others While ClpX/P is the major player, we recently found that ClpE/P is also involved in protein quality control in streptococci. However, the molecular mechanism of substrate recognition and degradation by ClpX/P and ClpE/P are not well understood in these organisms. In fact, very little is known about protein quality control and their role in virulence in streptococci. Our long-term goal is to understand the molecular mechanisms of regulated proteolysis in S. mutans and other oral streptococci.