Wille Holger, Requena Jesús R
Centre for Prions and Protein Folding Diseases & Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2M8, Canada.
CIMUS Biomedical Research Institute & Department of Medical Sciences, University of Santiago de Compostela-IDIS, 15782 Santiago de Compostela, Spain.
Pathogens. 2018 Feb 7;7(1):20. doi: 10.3390/pathogens7010020.
PrP (scrapie isoform of the prion protein) prions are the infectious agent behind diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (deer, elk, moose, and reindeer), as well as goat and sheep scrapie. PrP is an alternatively folded variant of the cellular prion protein, PrP, which is a regular, GPI-anchored protein that is present on the cell surface of neurons and other cell types. While the structure of PrP is well studied, the structure of PrP resisted high-resolution determination due to its general insolubility and propensity to aggregate. Cryo-electron microscopy, X-ray fiber diffraction, and a variety of other approaches defined the structure of PrP as a four-rung β-solenoid. A high-resolution structure of PrP still remains to be solved, but the four-rung β-solenoid architecture provides a molecular framework for the autocatalytic propagation mechanism that gives rise to the alternative conformation of PrP. Here, we summarize the current knowledge regarding the structure of PrP and speculate about the molecular conversion mechanisms that leads from PrP to PrP.
朊病毒蛋白（PrP，朊病毒蛋白的瘙痒病异构体）是人类克雅氏病、牛海绵状脑病、鹿科动物（鹿、麋鹿、驼鹿和驯鹿）慢性消耗病以及山羊和绵羊瘙痒病等疾病背后的传染因子。PrP是细胞朊病毒蛋白PrPC的一种可变折叠变体，PrPC是一种正常的、糖基磷脂酰肌醇锚定蛋白，存在于神经元和其他细胞类型的细胞表面。虽然PrPC的结构已得到充分研究，但由于PrP普遍不溶且易于聚集，其结构难以进行高分辨率测定。冷冻电子显微镜、X射线纤维衍射以及其他多种方法将PrP的结构确定为四股β-螺旋管。PrP的高分辨率结构仍有待解析，但四股β-螺旋管结构为导致PrP产生替代构象的自催化传播机制提供了分子框架。在此，我们总结了关于PrP结构的现有知识，并推测了从PrPC转变为PrP的分子转化机制。
