Structure of CfaA suggests a new family of chaperones essential for assembly of class 5 fimbriae.
Structure of CfaA suggests a new family of chaperones essential for assembly of class 5 fimbriae.
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DOI：
10.1371/journal.ppat.1004316
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发表时间：
2014-08
期刊：
影响因子：
6.7
通讯作者：
Xia D
中科院分区：
文献类型：
--
作者：
Bao R;Fordyce A;Chen YX;McVeigh A;Savarino SJ;Xia D
病原菌表面上的粘附性皮利包含聚合的菌毛蛋白亚基，并且对于感染的起始是必需的。皮利组装的伴侣引导途径（CUP）需要周质伴侣，协助亚基折叠，保持其稳定性，并护送他们的网站的生物组装。到目前为止，CUP分子伴侣已根据其F1和G1 β链之间的亚基相互作用环的短长度和长长度分别分为两个家族：FGS和FGL。CfaA是产肠球菌定植因子抗原I（CFA/I）皮利组装的分子伴侣。大肠杆菌（ETEC），这是旅行者和幼儿腹泻的一个原因。在这里，晶体结构的CfaA沿着与序列分析揭示了一些独特的结构和功能的特点，使我们提出一个单独的家庭CfaA和密切相关的伴侣。表型变化导致的独特的伴侣蛋白家族的区域中的突变提供了深入了解他们的功能，与这些地区的参与在菌毛组装过程中与同源亚基和引导蛋白的相互作用一致。细菌感染开始于微生物粘附到宿主细胞。对于革兰氏阴性菌，粘附通常由皮利介导，皮利是从细菌表面突出并识别宿主受体的蛋白质聚合物。在组装过程中，每个菌毛蛋白亚基通过分子伴侣辅助折叠，该分子伴侣将亚基穿梭到作为组装平台的外膜引导复合物。在那里，分子伴侣将其亚基货物转移到生长的菌毛聚合物中，菌毛聚合物突出于引导孔。在这里，我们提出了CFA/I菌毛的伴侣蛋白CfaA的晶体结构。CFA/I菌毛是肠致病性大肠杆菌的典型定植因子（CF），是低收入国家幼儿和前往这些地区的旅行者中危及生命的脱水性腹泻的主要原因。这种结构揭示了独特的功能，使我们能够定义一类新的伴侣，协助菌毛组装细菌。通过定点突变来探索这些独特的功能，我们能够对菌毛组装的机制有新的认识。
Adhesive pili on the surface of pathogenic bacteria comprise polymerized pilin subunits and are essential for initiation of infections. Pili assembled by the chaperone-usher pathway (CUP) require periplasmic chaperones that assist subunit folding, maintain their stability, and escort them to the site of bioassembly. Until now, CUP chaperones have been classified into two families, FGS and FGL, based on the short and long length of the subunit-interacting loops between its F1 and G1 β-strands, respectively. CfaA is the chaperone for assembly of colonization factor antigen I (CFA/I) pili of enterotoxigenic E. coli (ETEC), a cause of diarrhea in travelers and young children. Here, the crystal structure of CfaA along with sequence analyses reveals some unique structural and functional features, leading us to propose a separate family for CfaA and closely related chaperones. Phenotypic changes resulting from mutations in regions unique to this chaperone family provide insight into their function, consistent with involvement of these regions in interactions with cognate subunits and usher proteins during pilus assembly. Bacterial infection begins with microbial adhesion to host cells. For gram-negative bacteria, adhesion is often mediated by pili, proteinaceous polymers that protrude from the bacterial surface and recognize host receptors. During assembly, each pilus protein subunit is assisted in folding by a chaperone that shuttles the subunit to an outer membrane usher complex, which serves as assembly platform. There, the chaperone transfers its subunit cargo into the growing pilus polymer, which protrudes out the usher pore. Here, we present the crystal structure of CfaA, the chaperone protein of the CFA/I pilus. The CFA/I pilus is the archetypal colonization factor (CF) for enterotoxigenic Escherichia coli, a major cause of life-threatening, dehydrating diarrhea in young children of low-income countries and in travelers to these regions. This structure reveals unique features that allow us to define a new class of chaperones that assist pilus assembly in bacteria. Probing these unique features with site-direct mutagenesis, we were able to gain new insight into the mechanism of pilus assembly.
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革兰氏阴性细菌中非flagellar蛋白附加的结构和生物发生。
影响因子：
11.4
作者：
Fronzes, Remi;Remaut, Han;Waksman, Gabriel
通讯作者：
Waksman, Gabriel
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
64.8
作者：
HOLMGREN, A;BRANDEN, CI
通讯作者：
BRANDEN, CI
影响因子：
4.8
作者：
Li, Yong-Fu;Poole, Steven;Xia, Di
通讯作者：
Xia, Di
DOI：
10.1073/pnas.0812843106
发表时间：
2009-06-30
影响因子：
11.1
作者：
Li, Yong-Fu;Poole, Steven;Bullitt, Esther
通讯作者：
Bullitt, Esther