DETERMINING THE ARCHITECTURES OF MACROMOLECULAR ASSEMBLIES

确定大分子组装体的结构

• 批准号: 7954100
• 负责人: MICHAEL P ROUT
• 金额: $ 2.37万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954100
• 关键词: Architecture; Biological Models; Cell Nucleus; Cells; Collection; Computer Retrieval of Information on Scientific Projects Database; Data; Data Quality; Evolution; Funding; Grant; Institution; Life; Manuscripts; Maps; Nuclear Pore Complex; Paper; Process; Proteins; Proteomics; Publishing; Research; Research Personnel; Resources; Source; Structure; Translations; United States National Institutes of Health; Work; Yeasts; insight; macromolecular assembly; macromolecule; restraint

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. To understand the workings of a living cell, we need to know the architectures of its macromolecular assemblies. Here we show how proteomic data can be used to determine such structures. The process involves the collection of sufficient and diverse high-quality data, translation of these data into spatial restraints, and an optimization that uses the restraints to generate an ensemble of structures consistent with the data. Analysis of the ensemble produces a detailed architectural map of the assembly. We developed our approach on a challenging model system, the nuclear pore complex (NPC). The NPC acts as a dynamic barrier, controlling access to and from the nucleus, and in yeast is a 50 MDa assembly of 456 proteins. The resulting structure, presented in an accompanying paper, reveals the configuration of the proteins in the NPC, providing insights into its evolution and architectural principles. The present approach should be applicable to many other macromolecular assemblies. A manuscript describing thois approach has been published:

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 要了解活细胞的工作，我们需要了解其大分子组件的架构。在这里，我们展示了如何使用蛋白质组学数据来确定此类结构。该过程涉及收集足够多样化的高质量数据，将这些数据转换为空间限制，以及使用限制因素生成与数据一致的结构集合的优化。合奏的分析产生了组件的详细体系结构图。我们在挑战模型系统（NPC）上开发了我们的方法。 NPC充当动态障碍，控制对核的访问，而在酵母中是456个蛋白质的50 MDA组装。所得的结构在随附的论文中呈现，揭示了NPC中蛋白质的配置，从而提供了有关其进化和建筑原理的见解。本方法应适用于许多其他大分子组件。描述Thois方法的手稿已经发表：