STRUCTURAL CHARACTERIZATION OF PRION PROTEINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Prion病是由新型病原体Prion引起的一种独特的致命性神经退行性疾病。Prion的唯一成分是一种正常细胞蛋白的异常形式，称为Prion蛋白(PrP)。正常形式(PrPC)通过一个尚不清楚的翻译后过程转化为致病形式(PrPSc)。对于从生物组织、重组来源和多肽合成中分离的小规模PrP蛋白样品的详细分析，质谱学是必不可少的。一个目标是提高亚化学计量比修饰检测的灵敏度，因为众所周知，一个传染性的ID50包含数万个PrP分子，这些分子本身并不一定都是致病的。还有必要确定可能存在于传染性普恩病毒中的可能的辅助分子。还需要比较来自不同PrPSc菌株的PrPSc，以确定菌株的行为是否可能源于共价差异，例如N-连接的寡糖，这可能导致细胞特异性凝集素靶向有限范围的细胞类型，导致PrPSc的区域分布。到目前为止所获得的结果表明，参与PrPSc形成的PrPC的修饰可能是构象的，而不是化学的。

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.