HYBRID STRUCTURE DETERMINATION OF TRAFFICKING COMPLEXES BY SAXS, CRYSTALLOGRAPHY

通过 SAXS、晶体学测定贩运复合物的混合结构

• 批准号: 8362155
• 负责人: JAMES Bryant HURLEY
• 金额: $ 0.25万
• 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/8362155
• 关键词: Antigen Presentation; Biogenesis; Cereals; Complex; Core Assembly; Crystallography; Endosomes; Funding; Grant; HIV Budding; Homology Modeling; Hybrids; Individual; Membrane Protein Traffic; Modeling; National Center for Research Resources; Organelles; Pathway interactions; Physiological Processes; Principal Investigator; Process; Radiation; Research; Research Infrastructure; Resources; Series; Signal Transduction; Solutions; Source; Structure; United States National Institutes of Health; base; cost; protein complex; simulation; structural biology; trafficking

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. Membrane trafficking pathways are essential for normal physiological processes such as signal transduction, antigen presentation, organelle biogenesis, and many others, and for pathophysiological processes such as HIV budding. Membrane trafficking via endosomes is carried out by a series of multi-protein complexes, including the ESCRT complexes and the retromer complex. We have obtained a series of crystal structures of the cores of these assemblies, and in combination with the structures of individual domains and homology modeling, models for the complete structures can be generated. The models have been assessed by comparison to hydrodynamic studies of multiple truncation constructs, providing constraints on the solution structures of the intact complexes. We have applied coarse-grained Monte Carlo simulations using residue-based potentials with rigid domains and core structures to model the assemblies.

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。 膜运输途径对于正常的生理过程（例如信号转导、抗原呈递、细胞器生物发生等）以及病理生理过程（例如 HIV 出芽）至关重要。通过内体的膜运输是由一系列多蛋白复合物进行的，包括 ESCRT 复合物和逆转录酶复合物。我们获得了这些组件核心的一系列晶体结构，并结合各个域的结构和同源建模，可以生成完整结构的模型。通过与多个截断结构的流体动力学研究进行比较来评估模型，为完整复合物的溶液结构提供了约束。我们应用粗粒度蒙特卡罗模拟，使用具有刚性域和核心结构的基于残基的势来对组件进行建模。