STRUCTURAL AND FUNCTIONAL STUDIES OF P97

P97的结构和功能研究

• 批准号: 7721770
• 负责人: AXEL T BRUNGER
• 金额: $ 0.44万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721770
• 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.AlF(x)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。 我们正在追求p97的结构和功能研究（也称为VCP，含瓣膜蛋白的蛋白；古细菌中的VAT；酵母中的Cdc48），NSF的遥远同源物。 p97与内质网（ER）和高尔基体，核，凋亡和DNA复制的组装和生长的有丝分裂后同型膜融合有关。它还参与了泛素依赖性降解途径，以及从ER中提取错误折叠的腔和膜蛋白以进行胞质降解。我们最近使用SSRL和APS收集的衍射数据确定了与ADP和ADP.ALF（X）混合物复合的生物完整P97/VCP六聚体的晶体结构。在SSRL收集的MAD数据集提供了解决结构的密钥。 该结构揭示了单个域和连接链接器的四分之一配置。我们的晶体结构代表了P97/VCP的快照，因为它通过其核苷酸水解循环进行。我们的未来计划包括涉及p97/vcp的辅助蛋白和底物的复合物的结构研究，以阐明p97/vcp的机制和生物学作用。