LIPOPOLYSACCHARIDE TRANSPORT

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 革兰氏阴性细菌的外膜是重要的渗透性屏障，由不对称双层组成，其中内层小叶主要由磷脂组成，外层小叶主要由脂多糖（LPS）组成。 β-桶家族的外膜蛋白（OMP）跨越双层并充当通道和转运蛋白。使用化学遗传方法，我们最近鉴定了一种跨越周质的多蛋白复合物，负责 LPS 的组装。我们目前正在对这些蛋白质进行生化和结构研究，以了解疏水性 LPS 分子如何转运到 OM 的外叶并在其中组装。我们希望确定是否存在指导这种膜组装的一般原则，并表征抗生素开发的这些新蛋白质靶点。

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. The outer membrane of Gram-Negative Bacteria is an important permeability barrier that consists of an asymmetric bilayer in which the inner leaflet is primarily composed of phospholipids and the outer leaflet is primarily composed of lipopolysaccharides (LPS). Outer membrane proteins (OMPs) of the ?-barrel family span the bilayer and serve as channels and transporters. Using a chemical genetic approach, we recently identified a multi-protein complex that spans the periplasm that is responsible for the assembly of LPS. We are currently pursuing biochemical and structural studies of these proteins in order to understand how the hydrophobic LPS molecule is transported to and assembled in the outer leaflet of the OM. We hope to identify whether there are general principles that guide the assembly of this membrane and to characterize these new protein targets for antibiotic development.