ATOMIC STRUCTURE OF A PRP-FC FUSION PROTEIN

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。正常蛋白的修饰形式会引发传染性神经退行性疾病，如牛海绵状脑病(BSE)或人类的克雅氏病(CJD)。Prion蛋白被认为以两种不同的构象存在：“良性的”PrPc形式和具有感染性的“瘙痒形式”PrPsc。了解PrPc的三维结构对于理解向PrPsc的过渡是必不可少的。利用重组PrPc蛋白，核磁共振和X-射线结晶学已经解决了PrPc的C末端，但N末端是非结构化的。在这个方案中，我们将使用一个真核表达的融合蛋白PrP-Fc，通过X射线结晶学来解决PrPc的完整结构。

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. A modified form of normal prion protein triggers infectious neurodegenerative diseases, such as bovine spongiform encephalopathy (BSE), or Creutzfeldt-Jakob disease (CJD) in humans. Prion proteins are thought to exist in two different conformations: the 'benign' PrPc form, and the infectious 'scrapie form', PrPsc. Knowledge of the three-dimensional structure of PrPc is essential for understanding the transition to PrPsc. Using recombinant prion proteins, the C terminus of PrPc has been solved by NMR and x-ray crystallography, but the N terminus was found to be unstructured. In this proposal, we will employ an eukaryotically expressed fusion protein, PrP-Fc, to solve the complete structure of PrPc through x-ray crystallography.