SAXS STUDY OF NUCLEOTIDE-DEPENDENT CONFORMATIONAL CHANGE IN AB-TUBULIN AND HSP90

AB-微管蛋白和 HSP90 中核苷酸依赖性构象变化的 SAXS 研究

• 批准号: 7598147
• 负责人: DAVID A. AGARD
• 金额: $ 0.02万
• 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/7598147
• 关键词: Adopted; Binding; Computer Retrieval of Information on Scientific Projects Database; Eukaryotic Cell; Funding; Grant; Heat-Shock Proteins 90; Hydrolysis; Institution; Life; Measures; Microtubules; Molecular Chaperones; Molecular Conformation; Nucleotides; Protein Binding; Proteins; Research; Research Personnel; Resources; Roentgen Rays; Role; Source; Tubulin; United States National Institutes of Health; insight; preference; protein protein interaction; self assembly; tripolyphosphate

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. Ab-tubulin and the molecular chaperone HSP90 have essential non-overlapping roles in the life of eukaryotic cells. Both proteins bind and hydrolyze nucleotide triphosphates (GTP for tubulin, ATP for HSP90), and are known to adopt multiple conformations, as part of their functional cycle. It is not known, however, whether these conformational changes arise directly as a function of nucleotide state, or instead as a result of protein:protein interactions (self-assembly into microtubules for Ab-tubulin, substrate/co-chaperone binding in the case of HSP90). Studying how the conformations these of two different proteins respond to nucleotide state will be an essential first step in formulating a meaningful mechanistic understanding of their function. We propose to use small-angle X-ray scattering (SAXS) to measure scattering profiles as a function of nucleotide state, and thereby obtain vital structural insight into any potential changes in the conformational preferences of these proteins.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 Ab-微管蛋白和分子伴侣HSP 90在真核细胞的生命中具有重要的非重叠作用。 这两种蛋白质结合并水解三磷酸核苷酸（微管蛋白为GTP，HSP 90为ATP），并且已知采用多种构象作为其功能循环的一部分。然而，目前尚不清楚这些构象变化是否直接作为核苷酸状态的函数出现，或者作为蛋白质：蛋白质相互作用的结果（Ab-微管蛋白自组装成微管，HSP 90的情况下底物/共伴侣结合）。 研究两种不同蛋白质的构象如何响应核苷酸状态将是对它们的功能进行有意义的机械理解的重要第一步。 我们建议使用小角X射线散射（SAXS）来测量散射曲线作为核苷酸状态的函数，从而获得重要的结构洞察这些蛋白质的构象偏好的任何潜在变化。