HYBRID STRUCTURE DETERMINATION OF TRAFFICKING COMPLEXES BY SAXS, CRYSTALLOGRAPHY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 膜转运通路对于信号转导、抗原递呈、细胞器生物发生等正常生理过程以及HIV萌发等病理生理过程都是必不可少的。通过内体的膜转运是由一系列多蛋白复合体完成的，包括ESCRT复合体和逆转录病毒复合体。我们已经获得了这些组装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。通过与多个截断结构的流体力学研究进行比较，对这些模型进行了评估，为完整络合物的溶液结构提供了约束。我们应用了粗粒度的蒙特卡罗模拟，使用具有刚性结构域和核心结构的残基势来模拟组装。

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.