HYBRID STRUCTURE DETERMINATION OF TRAFFICKING COMPLEXES BY SAXS, CRYSTALLOGRAPHY

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。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。 膜运输途径对于正常生理过程如信号转导、抗原呈递、细胞器生物发生等以及对于病理生理过程如HIV出芽是必不可少的。通过内体的膜运输由一系列多蛋白复合物进行，包括ESCRT复合物和逆转录复合物。我们已经获得了这些组件的核心的一系列晶体结构，并结合单个结构域的结构和同源建模，可以生成完整结构的模型。该模型已进行了评估，通过比较多个截断结构的流体动力学研究，提供完整的复合物的解决方案的结构上的限制。我们已经应用粗粒度的蒙特卡罗模拟，使用基于残差的潜力与刚性域和核心结构的组件建模。

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.