GEOFF CHANG PRT-CRYSTALLOGRAPHY OF INTEGRAL MEMBRANE PROTEINS

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。 多药耐药是一个非常严重的健康问题，既有医学上的问题，也有药理学上的问题。多药耐药表型的原因是细胞内药物浓度净下降的结果。这种减少是通过两种基本机制发生的，一种是降低膜的通透性，从而导致药物进入脂质双层的速度降低(第I类)，另一种是直接增加药物从细胞中的去除率(第II类)。这两种机制都是通过一系列能量依赖的能量外排泵来实现的。最近，我们获得了第二类截然不同的MDR转运蛋白(第二类)的3D晶体。这项提议的目标是确定这些MDR转运体的原子结构。因此，我们将能够发现这个完整的膜蛋白家族多药耐药的结构基础。我们建议从我们的膜蛋白晶体中筛选和收集数据，并解决SSRL的MDR转运蛋白的结构。

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. Multi-drug resistance is a very significant health problem that has both medical and pharmacological concerns. The cause of the mdr phenotype is the result of a net decrease in the concentration of drug levels within the cell. This reduction occurs by two fundamental mechanisms that either lowers the membrane permeability, which leads to a decreased rate of drug entry across the lipid bilayer (Class I), or directly increasing the rate of drug removal from the cell (Class II). Both of these mechanisms are accomplished via a series of energy-dependent energy efflux pumps. Recently, we have obtained 3D crystals of a second distinct class of mdr transporters (Class II). The goal of this proposal is to determine the atomic structure of these mdr transporters. Hence, we will be able to discover the structural basis of mdr for this family of integral membrane proteins. We propose to screen and collect data from our membrane protein crystals and solve the structure of mdr transporter at SSRL.