STRUCTURAL ANALYSIS FOR THE ASSEMBLY MACHINERY FOR TYPE IV PILUS AND ITS RELATED

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。IV型菌毛（T4P）是暴露在革兰氏阴性菌表面的丝状结构。T4P是人类细菌病原体的关键毒力因子，包括铜绿假单胞菌、淋病奈瑟菌和霍乱弧菌。T4P丝是由一个亚基的10000个拷贝组成，该亚基具有高度保守的n端疏水序列，负责其组装。这一有趣的特征也见于不同细菌系统的其他亚基；II型分泌物和古菌鞭毛系统。这两个系统都含有类似T4P的亚基来形成丝。此外，这些系统中参与亚基组装的其他蛋白质彼此相似。其中，我们关注的是一个组装ATP酶家族，它利用ATP水解能组装肽亚基。我们一直在研究IV型菌毛亚基，已经解决了淋病奈瑟菌、铜绿假单胞菌和霍乱奈瑟菌菌毛亚基的晶体结构。在本论文中，我们将把双歧杆菌nodosus pilin作为不同类型的菌毛，P. aeruginosa XcpT作为II型分泌系统的丝亚基，afGspE2作为古菌鞭毛的组装atp酶进行结构解析。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type IV pili (T4P) are filamentous structures exposed on surface of Gram-negative bacteria. The T4P are key virulence factors for human bacterial pathogens including Pseudomonas aeruginosa, Neisseria gonorrhea, and Vibrio cholerae. T4P filament is composed of 10,000 of copies of a single subunit, which has a highly conserved N-terminal hydrophobic sequence, responsible for its assembly. This interesting feature is also seen in other subutnits in different bacterial systems; type II secretion and the archaeal flagellar system. Both systems also contain T4P like subunits to form filament. Furthermore, other proteins involved in the subunit assembly in these systems resemble with each other. Among them, we are focusing on an assembly ATPase family, which assemble pilin subunits utilizing ATP hydrolysis energy. We have been studying Type IV pilus subunit, and have solved the crystal structures of N. gonorrhea, P. aeruginosa, and V. cholerae pilin subunits. In this proposal, we will solve the structure of Dichelobactor nodosus pilin as different type of pilus, P. aeruginosa XcpT as filament subunit of type II secretion system, and afGspE2 as an assembly ATPase for archaeal flagellar.