The antigen 43 structure reveals a molecular Velcro-like mechanism of autotransporter-mediated bacterial clumping
The antigen 43 structure reveals a molecular Velcro-like mechanism of autotransporter-mediated bacterial clumping
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DOI：
10.1073/pnas.1311592111
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发表时间：
2014-01-07
影响因子：
11.1
通讯作者：
Schembri, Mark A.
中科院分区：
文献类型：
--
作者：
Heras, Begona;Totsika, Makrina;Schembri, Mark A.
聚集和生物膜形成是细菌对宿主免疫因子和抗生素产生抗性的关键机制。自转运蛋白（AT）是革兰氏阴性菌中最大的外膜蛋白和分泌蛋白，对这些表型有重要作用。尽管它们的丰度和细菌发病机制中的作用，大多数AT蛋白尚未进行结构表征，并且缺乏关于它们的作用模式的详细信息。在这里，我们报告的抗原43（Ag 43 a），一个原型的自缔合AT蛋白从尿路致病性大肠杆菌的结构与功能的关系。Ag 43 a的功能结构域显示出由3D氢键支架牢固稳定的扭曲的L形β-螺旋结构。值得注意的是，独特的Ag 43 a L形状促进自缔合和细胞聚集。结合我们所有的数据，我们定义了AT介导的细菌聚集的分子“Velcro样”机制，该机制可以定制以适应不同的细菌生活方式，例如生物膜的形成。
Aggregation and biofilm formation are critical mechanisms for bacterial resistance to host immune factors and antibiotics. Autotransporter (AT) proteins, which represent the largest group of outer-membrane and secreted proteins in Gram-negative bacteria, contribute significantly to these phenotypes. Despite their abundance and role in bacterial pathogenesis, most AT proteins have not been structurally characterized, and there is a paucity of detailed information with regard to their mode of action. Here we report the structure-function relationships of Antigen 43 (Ag43a), a prototypic self-associating AT protein from uropathogenic Escherichia coli. The functional domain of Ag43a displays a twisted L-shaped beta-helical structure firmly stabilized by a 3D hydrogen-bonded scaffold. Notably, the distinctive Ag43a L shape facilitates self-association and cell aggregation. Combining all our data, we define a molecular "Velcro-like" mechanism of AT-mediated bacterial clumping, which can be tailored to fit different bacterial lifestyles such as the formation of biofilms.