Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):457-62. doi: 10.1073/pnas.1311592111. Epub 2013 Dec 13.
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 β-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.
聚集和生物膜形成是细菌抵抗宿主免疫因子和抗生素的关键机制。自转运蛋白（AT）是革兰氏阴性菌中最大的外膜和分泌蛋白群，对这些表型有重要贡献。尽管它们大量存在且在细菌发病机制中发挥作用，但大多数 AT 蛋白的结构尚未得到明确表征，关于其作用模式的详细信息也很匮乏。在这里，我们报告了抗原 43（Ag43a）的结构-功能关系，Ag43a 是一种来自尿路致病性大肠杆菌的典型自缔合 AT 蛋白。Ag43a 的功能域呈现扭曲的 L 形 β-螺旋结构，由 3D 氢键支架牢固稳定。值得注意的是，Ag43a 的独特 L 形有助于其自身缔合和细胞聚集。综合我们所有的数据，我们定义了一个分子“魔术贴样”的 AT 介导的细菌聚集机制，它可以根据不同的细菌生活方式（如生物膜的形成）进行调整。
