STRUCTURAL STUDIES OF BACTERIAL PROTEIN COMPLEXES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 许多革兰氏阴性病原菌利用称为III型分泌系统（T3 SS）的复杂蛋白分泌装置将细菌效应蛋白转运到真核宿主细胞质中。易位子是T3 SS的结构组分，是穿过宿主细胞膜用于效应蛋白易位的蛋白质复合物。T3 SS蛋白转位的分子机制尚不清楚。我们的研究主要集中在志贺菌易位蛋白IpaB和IpaC及其伴侣IpgC的结构上。已经获得IpgC单晶，并且正在进行优化。组氨酸激酶已成为药物设计的有吸引力的新靶点，以规避革兰氏阳性病原菌的耐药性。我们的研究是针对一个多域，跨膜组氨酸激酶的结构和功能，从一个重要的双组分信号转导系统。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Many Gram-negative pathogenic bacteria employ a sophisticated protein secretion apparatus termed type III secretion system (T3SS) to transport bacterial effector proteins into eukaryotic host cytoplasm. The translocon, a structural component of T3SS, is a protein complex that traverses the host cell membrane for translocation of effector proteins. The molecular mechanisms underlying the T3SS protein translocation remain unclear. Our research is focused on the structures of Shigella translocon proteins IpaB and IpaC and their chaperone IpgC. IpgC single crystals have been obtained and optimization is underway. Histidine kinases have been attractive new targets for drug design to circumvent drug resistance in Grampositive pathogenic bacteria. Our research is aimed at structure and function of a multidomainal, membrane spanning histidine kinase from an essential two-component signal transduction system.