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: 8170103
• 负责人: JAMES Bryant HURLEY
• 金额: $ 0.38万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170103
• 关键词: Antigen Presentation; Biogenesis; Cereals; Complex; Computer Retrieval of Information on Scientific Projects Database; Core Assembly; Crystallography; Endosomes; Funding; Grant; HIV Budding; Homology Modeling; Hybrids; Individual; Institution; Membrane Protein Traffic; Modeling; Organelles; Pathway interactions; Physiological Processes; Process; Research; Research Personnel; Resources; Series; Signal Transduction; Solutions; Source; Structure; United States National Institutes of Health; base; protein complex; simulation; trafficking

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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。