Structures and Activities of Prions and Prion Proteins

朊病毒和朊病毒蛋白的结构和活性

• 批准号: 10014041
• 负责人: BYRON CAUGHEY
• 金额: $ 17.55万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10014041
• 关键词: Amyloid; Amyloid Fibrils; Amyloid Proteins; Bovine Spongiform Encephalopathy; Brain; Chronic Wasting Disease; Creutzfeldt-Jakob Syndrome; Cryoelectron Microscopy; Disease; Goals; Lateral; Molecular; Neurodegenerative Disorders; Pathogenesis; Pathologic; PrP; PrPSc Proteins; Prion Diseases; Resolution; Running; Scrapie; Structure; Vertebral column; base; beta pleated sheet; disease transmission; image reconstruction; synuclein; tau Proteins; transmission process

The structure of the infectious form of prion protein, PrPSc, remains unclear. One recent approach to solving protein amyloid fibril structures is cryo-electron microscopy, which has recently been used by other groups to reveal the amyloid core structures of disease-associated tau and synuclein fibrils. We have begun to pursue cryo-electron microscopy-based elucidation of PrPSc structure. Progress has been made, with lateral views and image reconstructions revealing stacked beta sheets running perpendicular to the fibril axis. The spacing between the sheets is 4.8 A. However, so far the resolution obtained has been insufficient to decipher the backbone folding of the core of amyloid fibrils of brain-derived PrPSc.

感染性朊病毒蛋白PrPSc的结构仍不清楚。最近解决蛋白质淀粉样纤维结构的一种方法是冷冻电子显微镜，其最近已被其他小组用于揭示疾病相关的tau和突触核蛋白纤维的淀粉样蛋白核心结构。我们已经开始追求基于冷冻电子显微镜的PrPSc结构的阐明。已经取得了进展，侧视图和图像重建显示堆叠的β片层垂直于原纤维轴。板之间的间距为4.8 A。然而，到目前为止，所获得的分辨率还不足以破译脑源性PrPSc的淀粉样纤维核心的骨架折叠。