The crystal structure of filamentous hemagglutinin secretion domain and its implications for the two-partner secretion pathway
The crystal structure of filamentous hemagglutinin secretion domain and its implications for the two-partner secretion pathway
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DOI：
10.1073/pnas.0400291101
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发表时间：
2004-04-20
影响因子：
11.1
通讯作者：
Villeret, V
中科院分区：
文献类型：
--
作者：
Clantin, B;Hodak, H;Villeret, V
丝状血凝素(FHA)是百日咳杆菌的主要粘附素，大小约为230 kDa，是革兰氏阴性杆菌分泌最多的蛋白质之一。FHA是通过双伴分泌(TPS)途径分泌的。几种重要的人类、动物和植物病原体也通过这种分泌方式分泌粘附素和其他毒力因子。TPS系统由两个独立的蛋白组成，TPSA是分泌蛋白，TPSB是相关的特异性外膜转运蛋白。所有TPS分泌的蛋白质都含有一个独特的N-近端模块，对分泌是必不可少的，即TPS结构域。我们报道了FHA功能分泌的30 kDa N-末端片段的1.7埃结构。它揭示了TPS结构域折叠成一个β-螺旋，有三个非螺旋基序，一个β-发夹，一个四链的β-折叠和一个N-末端封端，主要由TPS结构域的非保守区形成。因此，这种结构解释了为什么TPS结构域能够启动形成粘附素中心结构域的β-螺旋基序的折叠，因为它本身就是一个β-螺旋支架。它还包含保守程度较低的螺旋外区，最有可能参与特定性质，如识别外膜转运蛋白。这种结构代表了迄今为止在病原菌分泌蛋白>；100中发现的TPS结构域。它还为蛋白质折叠如何与TPS途径中的分泌相联系提供了一个机械性的见解。
Filamentous hemagglutinin (FHA), the major 230-kDa adhesin of the whooping cough agent Bordetella pertussis, is one of the most efficiently secreted proteins in Gram-negative bacteria. FHA is secreted by means of the two-partner secretion (TPS) pathway. Several important human, animal, and plant pathogens also secrete adhesins and other virulence factors by using this mode of secretion. A TPS system is composed of two separate proteins, with TpsA the secreted protein and TpsB its associated specific outermembrane transporter. All TPS-secreted proteins contain a distinctive N-proximal module essential for secretion, the TPS domain. We report here the 1.7-Angstrom structure of a functionally secreted 30-kDa N-terminal fragment of FHA. It reveals that the TPS domain folds into a beta-helix, with three extrahelical motifs, a beta-hairpin, a four-stranded beta-sheet, and an N-terminal capping, mostly formed by the nonconserved regions of the TPS domain. The structure thus explains why the TPS domain is able to initiate folding of the beta-helical motifs that form the central domain of the adhesin, because it is itself a beta-helical scaffold. It also contains less conserved extrahelical regions most likely involved in specific properties, such as the recognition of the outer-membrane transporter. This structure is representative of the TPS domains found so far in >100 secreted proteins from pathogenic bacteria. It also provides a mechanistic insight into how protein folding may be linked to secretion in the TPS pathway.