LIPOPOLYSACCHARIDE TRANSPORT

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。 革兰氏阴性菌的外膜是一种重要的通透性屏障，它由一个不对称的双层组成，内叶主要由磷脂组成，外叶主要由脂多糖(LPS)组成。外膜蛋白家族的外膜蛋白(OMP)跨越双分子层，作为通道和转运体。利用化学遗传学方法，我们最近发现了一个跨越周质的多蛋白复合体，它负责组装内毒素。我们目前正在对这些蛋白质进行生化和结构研究，以了解疏水性内毒素分子是如何运输到OM外叶并组装到OM的外叶中的。我们希望确定是否有指导这种膜组装的一般原则，并表征这些用于抗生素开发的新蛋白质靶点。

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.