DETERMINATION OF THE PSEUDO-ATOMIC STRUCTURE OF NUCLEAR PORE COMPLEX (NPC) COMPO

核孔复合体（NPC）复合物拟原子结构的测定

• 批准号: 8362329
• 负责人: ANDREJ SALI
• 金额: $ 1.45万
• 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/8362329
• 关键词: Architecture; Cell physiology; Complex; Computer software; Data; Funding; Genetic Transcription; Grant; Human; Malignant Neoplasms; Maps; Modeling; National Center for Research Resources; Nuclear Envelope; Nuclear Pore Complex; Nuclear Pore Complex Proteins; Play; Positioning Attribute; Principal Investigator; Proteins; Protocols documentation; Radiation; Relative (related person); Research; Research Infrastructure; Resolution; Resources; Sampling; Source; Structure; Tertiary Protein Structure; United States National Institutes of Health; Work; Yeasts; base; cost; human disease; improved; macromolecule; restraint; structural biology; three dimensional structure

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. The Nuclear Pore Complex (NPC, about 50 MDa) is the sole passageway for the transport of macromolecules across the nuclear envelope. The pore plays a key role in numerous critical cellular processes such as transcription, and many of its components are implicated in human diseases such as cancer. Previous work provided the first description of the macromolecular architecture of the yeast NPC. This structure defined the relative positions and proximities of its 456 constituent nucleoporin (nup) proteins, based on spatial restraints derived from experimental data. Further elucidation of the evolutionary origin and transport mechanism of the NPC will require higher resolution information. To help improve upon the resolution and accuracy of the NPC structure, we propose to obtain small angle x-ray scattering (SAXS) data at SSRL. We are preparing a set of single protein, protein domain, and small NPC subcomplex samples for SAXS analysis. We will apply our Integrated Modeling Platform (IMP) software to incorporate a diverse set of experimental data, including SAXS spectra, as spatial restraints, to determine the three dimensional structures of these subcomplexes and proteins. We are specifically focusing on components of two subcomplexes, the 7-protein Nup84 subcomplex, and the 4-protein Nup170 complex, for which complementary experimental data are available. We have already used a similar protocol, to map different functional states of human Hsp90.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 核孔复合物（NPC，约50 MDA）是大分子横跨核包膜的唯一通道。该孔在许多关键细胞过程（例如转录）中起着关键作用，其许多成分与人类疾病（如癌症）有关。先前的工作提供了酵母NPC大分子结构的首次描述。该结构基于从实验数据得出的空间约束，定义了其456个组成核蛋白（NUP）蛋白的相对位置和接近性。 NPC的进化起源和运输机制的进一步阐明将需要更高的分辨率信息。为了帮助提高NPC结构的分辨率和准确性，我们建议在SSRL上获得小角度X射线散射（SAXS）数据。我们正在准备一组单一蛋白质，蛋白质结构域和小型NPC亚复合样品，以进行SAXS分析。我们将应用我们的集成建模平台（IMP）软件，将一组各种实验数据（包括SAXS Spectra，作为空间约束）确定，以确定这些子复合物和蛋白质的三维结构。我们特别关注两个子复合物的组件，即7-蛋白NUP84子复合物和4-蛋白NUP170复合物，为此提供了互补的实验数据。我们已经使用了类似的协议来映射人类HSP90的不同功能状态。