STRUCTURE AND MECHANISM OF CS1 PILUS ASSEMBLY

CS1 PILUS组件的结构和机构

• 批准号: 7720683
• 负责人: James G. Bann
• 金额: $ 5.22万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720683
• 关键词: Adherence; Binding; Cell surface; Cells; Child; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Developing Countries; Disease; Distal; Escherichia coli Infections; Fiber; Funding; Grant; Hair; Human; Infant; Institution; Intestines; Mediating; Membrane Proteins; Molecular Chaperones; Morbidity - disease rate; Operon; Pilum; Research; Research Personnel; Resources; Role; Source; Structure; Surface; System; Tissues; United States National Institutes of Health; base; design; enterotoxigenic Escherichia coli; novel; pathogenic bacteria; periplasm; polymerization

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. Pili are hair-like surface fibers that mediate attachment and colonization of pathogenic bacteria to host tissues. The CS1 pilus system from enterotoxigenic Escherichia coli (ETEC) is required for the establishment and colonization of ETEC to the human intestine, resulting in diarrheal disease that is a significant cause of morbidity in infants and children in third-world countries. CS1 is encoded on the cooBACD operon, and is composed of multiple CooA subunits that have at the distal tip the single subunit of CooD that is required for adherence to intestinal cells. Additionally, CooC, a 95-kDa outer membrane protein, and CooB, a periplasmic chaperone, are required for pilus assembly. The specific hypothesis is that the assembly of CS1 pili is initiated by a conformational change in the outer membrane protein CooC upon binding of CooB alone are as a complex with CooD or CooA. The hypothesis is based on data that indicate that 1) CooC is an integral outer membrane protein, 2) expression of CooC is required for export of pili to the cell surface and 3) CooB co-purifies with CooC and stabilizes CooC against proteolytic degradation. Therefore CooB, either by itself or as a complex with CooA or CooD, initiates a conformational change in CooC that allows transport of subunits to the surface. The specific aims of our research are: 1. Characterize the native structure and oligomerization state of CooB. 2. Define structural changes in CooC. 3. Determine the role of CooC in the mechanism of polymerization of CooA. Information obtained from these studies may be useful in the design of novel therapies that provide protection against ETEC infection.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 pili是头发样的表面纤维，可介导致病细菌与宿主组织的附着和定植。 来自肠毒素大肠杆菌（ETEC）的CS1菌毛系统是将ETEC建立和定殖对人类肠道的建立和定殖所必需的，这导致腹泻病，这是第三世界国家婴儿和儿童发病率的重要原因。 CS1编码在COOBACD操纵子上，由多个COOA亚基组成，这些亚基在远端具有COOD的单个亚基，这是遵守肠道细胞所需的。 另外，菌毛组装需要COOC，一种95 kDa外膜蛋白，而COOB（一种阴性伴侣）。特定的假设是，CS1 PILI的组装是通过单独使用COOB结合后的外膜蛋白COOC的构象变化引发的，就像COOD或COOA一样的复合物。该假设基于数据表明1）COOC是一种积分的外膜蛋白，2）COOC表达pili需要将Pili出口到细胞表面，而3）COOB COOB用COOC进行COOC，并稳定COOC，以稳定COOC，以稳定蛋白水解降解。 因此，COOB本身或作为COOA或COOD的复合物，都会引发COOC中的构象变化，允许将亚基运输到表面。我们研究的具体目的是：1。表征COOB的天然结构和低聚状态。 2。定义COOC的结构变化。 3。确定COOC在COOA聚合机理中的作用。 从这些研究中获得的信息可能在设计可保护ETEC感染的新型疗法的设计中很有用。