GEOFF CHANG PRT-CRYSTALLOGRAPHY OF INTEGRAL MEMBRANE PROTEINS

Geoff Chang PRT-完整膜蛋白的晶体学

• 批准号: 8362052
• 负责人: GEOFFREY A CHANG
• 金额: $ 0.36万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362052
• 关键词: Cell Membrane Permeability; Cells; Crystallography; Data; Excision; Family; Funding; Goals; Grant; Health; Integral Membrane Protein; Lipid Bilayers; Medical; Membrane Proteins; Multi-Drug Resistance; National Center for Research Resources; Pharmaceutical Preparations; Phenotype; Principal Investigator; Radiation; Research; Research Infrastructure; Resources; Series; Source; Structure; United States National Institutes of Health; base; cost; efflux pump; structural biology

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.

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。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 多药耐药性是一个非常重要的健康问题，具有医学和药理学关注。mdr表型的原因是细胞内药物浓度水平净下降的结果。这种减少通过两种基本机制发生，即降低膜渗透性，导致药物穿过脂质双层的速率降低（I类），或直接增加药物从细胞中去除的速率（II类）。这两种机制都是通过一系列依赖能量的能量外排泵来实现的。最近，我们已经获得了第二类不同的MDR转运蛋白（II类）的3D晶体。这项计划的目标是确定这些多药耐药转运蛋白的原子结构。因此，我们将能够发现这个完整的膜蛋白家族的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，并在SSRL解决MDR转运蛋白的结构。