STRUCTURAL STUDIES OF BACTERIAL PROTEIN COMPLEXES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 许多革兰氏阴性致病菌利用一种被称为III型分泌系统(T3SS)的复杂的蛋白质分泌装置将细菌效应蛋白输送到真核宿主细胞质中。转位蛋白是T3SS的一个结构成分，是一种穿过宿主细胞膜进行效应蛋白转位的蛋白质复合体。T3SS蛋白易位的分子机制尚不清楚。我们的研究重点是志贺氏菌转位蛋白IPAB和IPAC及其伴侣蛋白IpgC的结构。获得了IPgC单晶，并对其进行了优化。组氨酸激酶已成为革兰氏阳性病原菌耐药药物设计的新靶点。我们的研究旨在从一个基本的双组分信号转导系统中获得一个多结构域、跨膜的组氨酸激酶的结构和功能。

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.