STRUCTURAL CHARACTERIZATION OF PRION PROTEINS

朊病毒蛋白的结构表征

• 批准号: 8363722
• 负责人: STANLEY B PRUSINER
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363722
• 关键词: Behavior; Biological; Cells; Chemicals; Detection; Funding; Grant; Lectin; Link; Mass Spectrum Analysis; Modification; National Center for Research Resources; Neurodegenerative Disorders; Oligosaccharides; Peptide Synthesis; PrPSc Proteins; Principal Investigator; Prion Diseases; Prions; Process; Proteins; Recombinants; Research; Research Infrastructure; Resources; Sampling; Source; Tissues; United States National Institutes of Health; cell type; cost; novel; pathogen

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. 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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 朊病毒病是由朊病毒引起的一种独特的致命性神经退行性疾病。朊病毒的唯一组成部分是一种称为朊病毒蛋白（PrP）的正常细胞蛋白质的异常形式。正常形式（PrPC）通过一个尚未确定的翻译后过程转化为致病形式（PrPSc）。质谱法对于从生物组织、重组来源和肽合成中分离的朊病毒蛋白的小规模样品的详细分析至关重要。一个目的是增加检测亚化学计量修饰的灵敏度，因为已知感染性的一个ID 50含有数万个PrP分子，并非所有这些分子本身都必然是致病性的。也有必要鉴定可能存在于感染性朊病毒中的可能的辅助分子。还需要比较来自不同朊病毒株的PrPSc，以确定菌株行为是否可能源于共价差异，例如N-连接寡糖，这可能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。到目前为止获得的结果表明，在PrPSc的形成所涉及的PrPC的修改可能是构象，而不是化学。