STRUCTURAL AND FUNCTIONAL STUDIES OF P97

P97的结构和功能研究

• 批准号: 7597969
• 负责人: AXEL T BRUNGER
• 金额: $ 0.61万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7597969
• 关键词: Apoptosis; Archaea; Biological; Cell Nucleus; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA biosynthesis; Data; Data Set; Degradation Pathway; Distant; Endoplasmic Reticulum; Funding; Future; Golgi Apparatus; Grant; Growth; Homologous Gene; Hydrolysis; Individual; Institution; KLK3 gene; Membrane Fusion; Membrane Proteins; Nucleotides; Research; Research Personnel; Resources; Role; Source; Structure; Ubiquitin; United States National Institutes of Health; Yeasts; adapter protein; luminal membrane; valosin-containing protein

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. We are pursuing structural and functional studies of p97 (also called VCP, valosin-containing protein; VAT in Archaebacteria; and cdc48 in yeast), a distant homolog of NSF. p97 has been implicated in postmitotic homotypic membrane fusion of the endoplasmic reticulum (ER) and of the Golgi apparatus, assembly and growth of the nucleus, apoptosis, and DNA replication. It is also involved in the ubiquitin-dependent degradation pathway, as well as the extraction of misfolded luminal and membrane proteins from the ER for cytosolic degradation. We recently determined the crystal structure of the biologically complete p97/VCP hexamer complexed with a mixture of ADP and ADP.AlFx using diffraction data collected at SSRL and APS. The MAD dataset collected at SSRL provided the key to solve the structure. The structure revealed the quarternary configuration of the individual domains and the connecting linkers. Our crystal structure represents a snapshot of p97/VCP as it proceeds through its nucleotide hydrolysis cycle. Our future plans include structural studies of complexes involving adapter proteins and substrates for p97/VCP, to elucidate the mechanism and biological role of p97/VCP.

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。 我们正在对 p97（也称为 VCP，含 valosin 的蛋白质；古细菌中的 VAT；以及酵母中的 cdc48）进行结构和功能研究，p97 是 NSF 的远亲同源物。 p97 参与内质网 (ER) 和高尔基体的有丝分裂后同型膜融合、细胞核的组装和生长、细胞凋亡和 DNA 复制。它还参与泛素依赖性降解途径，以及从内质网中提取错误折叠的管腔蛋白和膜蛋白进行胞质降解。我们最近使用 SSRL 和 APS 收集的衍射数据确定了生物学上完整的 p97/VCP 六聚体与 ADP 和 ADP.AlFx 混合物复合的晶体结构。 SSRL 收集的 MAD 数据集提供了解决该结构的关键。 该结构揭示了各个结构域和连接子的四元构型。我们的晶体结构代表了 p97/VCP 在核苷酸水解循环中的快照。我们未来的计划包括对涉及 p97/VCP 接头蛋白和底物的复合物进行结构研究，以阐明 p97/VCP 的机制和生物学作用。