Complete fiber structures of complex trimeric autotransporter adhesins conserved in enterobacteria
Complete fiber structures of complex trimeric autotransporter adhesins conserved in enterobacteria
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DOI：
10.1073/pnas.1211872110
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发表时间：
2012-12-18
影响因子：
11.1
通讯作者：
Alvarez, Birte Hernandez
中科院分区：
文献类型：
--
作者：
Hartmann, Marcus D.;Grin, Iwan;Alvarez, Birte Hernandez
三聚体自转运粘附素（TAAs）是一种高度重复的模块化表面蛋白，其在广泛的革兰氏阴性病原体中介导与宿主细胞的粘附。尽管它们的大小可能相差超过一个数量级，但它们都遵循相同的基本头部-柄部-锚结构，其中头部介导粘附和自凝集，柄部将头部从细菌表面突出，并且锚提供输出功能并在输出完成后将粘附素附着到细菌外膜。在复杂的粘附素中，在到达锚之前，头部和柄部结构域可以交替几次。尽管存在广泛的序列差异，但由于其组成多肽链的紧密交织，TAA结构域的结构受到高度限制。因此，我们采取了“域字典”的方法来表征代表每一个域类型的X射线晶体学和使用这些结构来重建完整的TAA纤维。分别用沙门氏菌SadA、致病性大肠杆菌EhaG和致病性大肠杆菌UpaG对大肠杆菌进行酶联免疫吸附试验。大肠杆菌（UPEC），我们提出了一个复杂的粘附素，发生在一个保守的基因组环境中的肠杆菌和尿路致病性大肠杆菌的感染过程中必不可少的三个代表性结构。杆菌我们的工作证明了字典方法的适用性，以了解一类蛋白质的结构，否则难以处理的高分辨率的方法，并提供了一个基础，快速和详细的注释新确定的TAAs。
Trimeric autotransporter adhesins (TAAs) are modular, highly repetitive surface proteins that mediate adhesion to host cells in a broad range of Gram-negative pathogens. Although their sizes may differ by more than one order of magnitude, they all follow the same basic head-stalk-anchor architecture, where the head mediates adhesion and autoagglutination, the stalk projects the head from the bacterial surface, and the anchor provides the export function and attaches the adhesin to the bacterial outer membrane after export is complete. In complex adhesins, head and stalk domains may alternate several times before the anchor is reached. Despite extensive sequence divergence, the structures of TAA domains are highly constrained, due to the tight interleaving of their constituent polypeptide chains. We have therefore taken a "domain dictionary" approach to characterize representatives for each domain type by X-ray crystallography and use these structures to reconstruct complete TAA fibers. With SadA from Salmonella enterica, EhaG from enteropathogenic Escherichia coli (EHEC), and UpaG from uropathogenic E. coli (UPEC), we present three representative structures of a complex adhesin that occur in a conserved genomic context in Enterobacteria and is essential in the infection process of uropathogenic E. coli. Our work proves the applicability of the dictionary approach to understanding the structure of a class of proteins that are otherwise poorly tractable by high-resolution methods and provides a basis for the rapid and detailed annotation of newly identified TAAs.