FIBER DIFFRACTION FROM MAMMALIAN PRIONS

哺乳动物朊病毒的纤维衍射

• 批准号: 7954387
• 负责人: Gerald J Stubbs
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954387
• 关键词: Alzheimer' s Disease; Amyloid; Amyloid fibers; Amyloidosis; Bovine Spongiform Encephalopathy; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Creutzfeldt-Jakob Syndrome; Crystallography; Drug Design; Electron Microscopy; Fiber; Filament; Funding; Grant; Hereditary Amyloidosis; Institution; Methods; Molecular Conformation; Non-Insulin-Dependent Diabetes Mellitus; PrP; Prion Diseases; Prions; Process; Proteins; Research; Research Personnel; Resources; Scrapie; Source; Structure; United States National Institutes of Health; amyloid formation; protein aggregate; protein folding; structural biology; synchrotron radiation

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. Amyloid fibers are formed when normally soluble proteins change conformation to form insoluble filaments that can cause severe damage and even death. Amyloidoses include Alzheimer's disease, type II diabetes, hereditary amyloidoses, and a variety of prion diseases including Creutzfeldt-Jakob disease, BSE ("mad cow disease"), and scrapie. Mammalian prions are infectious protein aggregates formed by the prion protein PrP when it folds into aberrant structures. Amyloids - by definition - share a cross-beta structure, but the structural details are not known. Amyloid fibers have resisted characterization by crystallography and NMR. Fiber diffraction is an effective method for determining the structural details of filamentous assemblies, and in combination with electron microscopy offers the best hope for elucidating the structures of prions and other amyloids. Structural studies are needed to answer fundamental protein folding questions, to understand the process of amyloid formation, and for rational drug design.

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。 淀粉样纤维是在正常可溶性蛋白质改变构象形成不溶性细丝时形成的，这些细丝可导致严重损伤甚至死亡。淀粉样变性包括阿尔茨海默病、II型糖尿病、遗传性淀粉样变性和多种朊病毒疾病，包括克雅氏病、疯牛病和羊瘙痒病。哺乳动物朊病毒是由朊病毒蛋白PrP折叠成异常结构时形成的感染性蛋白质聚集体。根据定义，淀粉样蛋白具有交叉β结构，但结构细节尚不清楚。淀粉样纤维抵抗晶体学和NMR的表征。纤维衍射是一种有效的方法，用于确定丝状组件的结构细节，并结合电子显微镜提供了最好的希望，阐明朊病毒和其他淀粉样蛋白的结构。结构研究需要回答基本的蛋白质折叠问题，了解淀粉样蛋白形成的过程，以及合理的药物设计。