STRUCTURAL CHARACTERIZATION OF PRION PROTEINS

朊病毒蛋白的结构表征

• 批准号: 8169717
• 负责人: STANLEY B PRUSINER
• 金额: $ 0.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-12 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169717
• 关键词: Behavior; Biological; Cells; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Detection; Funding; Grant; Institution; Lectin; Link; Mass Spectrum Analysis; Modification; Neurodegenerative Disorders; Oligosaccharides; Peptide Synthesis; PrPSc Proteins; Prion Diseases; Prions; Process; Proteins; Recombinants; Research; Research Personnel; Resources; Sampling; Source; Tissues; United States National Institutes of Health; cell type; novel; pathogen

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. Prion diseases are unique fatal neurodegenerative diseases caused by novel pathogens termed prions. The only component of prions is an abnormal form of a normal cellular protein termed the prion protein (PrP). The normal form (PrPC) is converted to the pathogenic form (PrPSc) by an as yet unidentified posttranslational process. Mass spectrometry is essential for the detailed analysis of small-scale samples of the prion protein isolated from biological tissues, from recombinant sources and from peptide synthesis. One objective is increase the sensitivity for detection of sub-stoichiometric modifications as it is known that one ID50 of infectivity contains tens of thousands of PrP molecules, not all of which are necessarily pathogenic in their own right. It is also necessary to identify possible accessory molecules that might be present in infectious prions. Comparisons are also required between PrPSc from different prion strains to establish whether strain behavior could arise from covalent differences, e.g. in the N-linked oligosaccharides, which might cause cell specific lectins to target a limited range of cell types, resulting in regional distribution of PrPSc. Results obtained so far suggest that the modification of PrPC involved in the formation of PrPSc is likely conformational rather than chemical.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 朊病毒病是一种独特的致命性神经退行性疾病，由称为朊病毒的新型病原体引起。朊病毒的唯一成分是正常细胞蛋白的异常形式，称为朊病毒蛋白（PrP）。正常形式 (PrPC) 通过尚未确定的翻译后过程转化为致病形式 (PrPSc)。质谱对于从生物组织、重组来源和肽合成中分离的小规模朊病毒蛋白样品的详细分析至关重要。一个目标是提高检测亚化学计量修饰的灵敏度，因为已知感染性的一个 ID50 包含数以万计的 PrP 分子，但并非所有这些分子本身都必然具有致病性。还必须确定传染性朊病毒中可能存在的辅助分子。还需要对来自不同朊病毒株的 PrPSc 进行比较，以确定应变行为是否可能由共价差异引起，例如N 连接寡糖中的蛋白质，这可能会导致细胞特异性凝集素靶向有限范围的细胞类型，从而导致 PrPSc 的区域分布。迄今为止获得的结果表明，参与 PrPSc 形成的 PrPC 修饰可能是构象修饰，而不是化学修饰。