HUMAN SMALL HEAT SHOCK PROTEINS AND THEIR PH-DEPENDENT ACTIVATION

人类小热休克蛋白及其 PH 依赖性激活

• 批准号: 8362369
• 负责人: PONNI RAJAGOPAL
• 金额: $ 0.08万
• 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/8362369
• 关键词: Crystallins; Data; Disease; Funding; Grant; HSPB1 gene; Heat shock proteins; Homeostasis; Human; Inherited; Manuscripts; Measures; National Center for Research Resources; Principal Investigator; Proteins; Radiation; Research; Research Infrastructure; Resources; Sampling; Shapes; Solutions; Source; Stress; Structure; System; Temperature; United States National Institutes of Health; alpha-Crystallins; cost; mutant; structural biology

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. We would like to determine the shape of homodimeric, 90-residue alpha- crystallin domains from A;B-Crystallin (A;B) and HSP27 under different conditions of pH. A-crystallin domains are conserved domains in highly oligomeric small Heat Shock Proteins (sHSPs, e.g. A;B and HSP27) that help maintain protein homeostasis as part of the cellular protection system against stress such as changes in temperature or pH. pH-dependent structural changes are observed in the wild type (wt) A-crystallin domain from A;B and not observed in an inherited disease-associated missense mutant, R120G. Our solution state NMR studies show that the structure of the wt and mutant domains are essentially the same at neutral pH. We hypothesize that the shapes of the domains may undergo a pH-dependent change that drives the changes observed in oligomers. We are currently calculating and refining solution-state structures of the A-crystallin domains in anticipation of submitting a manuscript in late spring. Our plan is to include SAXS data collected on samples as a function of pH as an independent measure of pH-induced structural changes.

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。 我们想在pH的不同条件下从A; B-晶状体（A; B）和HSP27的同型二聚体，90个残留α-晶体结构域的形状。 A-晶体蛋白结构域是高度寡聚的小热激蛋白（SHSP，例如A; B和HSP27）中的保守结构域，有助于维持蛋白质稳态，这是细胞保护系统的一部分，以防止诸如温度或pH的变化等压力。 pH依赖性的结构变化是在a; b的野生型（WT）A-晶状体结构域中观察到的，而在遗传性疾病相关的错义突变体R120G中未观察到。 我们的溶液状态NMR研究表明，在中性pH值下，WT和突变域的结构基本相同。我们假设域的形状可能会发生pH依赖性变化，从而驱动在低聚物中观察到的变化。目前，我们正在计算和完善A-Crystallin域的解决方案状态结构，以期在春季晚些时候提交手稿。 我们的计划是包括在样品上收集的SAXS数据作为pH的函数，作为pH诱导的结构变化的独立度量。