3D structure/function analysis of PiIX reveals how minor pilins can modulate the virulence properties of type IV pili
3D structure/function analysis of PiIX reveals how minor pilins can modulate the virulence properties of type IV pili
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DOI：
10.1073/pnas.0707581104
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发表时间：
2007-10-02
影响因子：
11.1
通讯作者：
Forest, Katrina T.
中科院分区：
文献类型：
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作者：
Helaine, Sophie;Dyer, David H.;Forest, Katrina T.
IV型菌毛(TFP)是广泛存在的丝状细菌细胞器，介导多种毒力相关表型。它们主要由菌毛蛋白亚基组成，在细丝组装之前由专门的预毛蛋白多肽酶进行加工。由这些肽酶加工的其他蛋白质，其分子性质和作用方式仍然是个谜，在TFP生物学中发挥着关键作用。我们已经对脑膜炎奈瑟氏菌的其中一种蛋白质PiIX进行了详细的结构/功能分析，它对细菌聚集体的形成和与人类细胞的黏附至关重要。PiIX的X射线晶体结构表明，所有Pilins都有α/β卷曲，我们表明该蛋白与TFP共定位。这些观察结果表明，PiIX是一种少量或低丰度的菌毛素，它以类似于菌毛素的方式在细丝内组装。预计将暴露在细丝表面的PiIX独特结构元件的缺失，取消了聚集和粘连。我们的结果支持一个模型，在该模型中，PiIX亚单位中暴露在表面的基序稳定了细菌聚集体，使其免受菌毛回缩的破坏力的影响，并说明了微小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。
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, PiIX from Neisseria meningitidis, which is crucial for formation of bacterial aggregates and adhesion to human cells. The x-ray crystal structure of PiIX reveals the alpha/beta roll fold shared by all pilins, and we show that this protein colocalizes with Tfp. These observations suggest that PiIX is a minor, or low abundance, pilin that assembles within the filaments in a similar way to pilin. Deletion of a PiIX 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 PiIX 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.