Helaine Sophie, Dyer David H, Nassif Xavier, Pelicic Vladimir, Forest Katrina T
Institut National de la Santé et de la Recherche Médicale, U570, 75015 Paris, France.
Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15888-93. doi: 10.1073/pnas.0707581104. Epub 2007 Sep 24.
Type IV pili (Tfp) are widespread filamentous bacterial organelles that mediate multiple virulence-related phenotypes. They are composed mainly of pilin subunits, which are processed before filament assembly by dedicated prepilin peptidases. Other proteins processed by these peptidases, whose molecular nature and mode of action remain enigmatic, play critical roles in Tfp biology. We have performed a detailed structure/function analysis of one such protein, PilX from Neisseria meningitidis, which is crucial for formation of bacterial aggregates and adhesion to human cells. The x-ray crystal structure of PilX reveals the alpha/beta roll fold shared by all pilins, and we show that this protein colocalizes with Tfp. These observations suggest that PilX is a minor, or low abundance, pilin that assembles within the filaments in a similar way to pilin. Deletion of a PilX distinctive structural element, which is predicted to be exposed on the filament surface, abolishes aggregation and adhesion. Our results support a model in which surface-exposed motifs in PilX subunits stabilize bacterial aggregates against the disruptive force of pilus retraction and illustrate how a minor pilus component can enhance the functional properties of pili of rather simple composition and structure.
IV型菌毛（Tfp）是广泛存在的丝状细菌细胞器，介导多种与毒力相关的表型。它们主要由菌毛蛋白亚基组成，这些亚基在丝状组装前由专门的前菌毛蛋白酶进行加工。由这些蛋白酶加工的其他蛋白质，其分子性质和作用方式仍然是个谜，但在Tfp生物学中起着关键作用。我们对其中一种蛋白质进行了详细的结构/功能分析，这种蛋白质来自脑膜炎奈瑟菌，名为PilX，对细菌聚集和黏附于人体细胞至关重要。PilX的X射线晶体结构揭示了所有菌毛蛋白共有的α/β卷曲折叠，并且我们表明这种蛋白质与Tfp共定位。这些观察结果表明，PilX是一种次要的或低丰度的菌毛蛋白，它以与菌毛蛋白相似的方式在丝状物中组装。删除PilX一个独特的结构元件，预计该元件会暴露在丝状物表面，会消除聚集和黏附。我们的结果支持这样一种模型，即PilX亚基中暴露于表面的基序可稳定细菌聚集体，抵抗菌毛收缩的破坏力，并说明了一种次要的菌毛成分如何增强组成和结构相当简单的菌毛的功能特性。
