LIPOPOLYSACCHARIDE TRANSPORT

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。 为子项目列出的总成本可能 表示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。 革兰氏阴性菌的外膜是一种重要的渗透屏障，由不对称双层组成，其中内小叶主要由磷脂组成，外小叶主要由脂多糖（LPS）组成。外膜蛋白（OMP）的？-桶家族跨越双层并充当通道和转运体。使用化学遗传学方法，我们最近确定了一个多蛋白质复合物，跨越周质，负责LPS的组装。我们目前正在进行这些蛋白质的生物化学和结构研究，以了解疏水性LPS分子是如何转运到OM的外小叶并在OM的外小叶中组装的。我们希望确定是否存在指导这种膜组装的一般原则，并描述这些新的蛋白质靶点用于抗生素开发。

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.