Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Center for Advanced Study, Shandong University of Technology, Zibo 255049, PR China.
Trends Biochem Sci. 2010 Mar;35(3):129-34. doi: 10.1016/j.tibs.2009.12.002. Epub 2010 Jan 7.
Structural information regarding normal prion protein (PrP(C)) and the scrapie isoform (PrP(Sc)) is of vital importance for elucidating the pathogenesis of prion diseases (PDs). Despite successful determination of the three-dimensional structures of PrP(C), the structural details of PrP(Sc) remain elusive. Nevertheless, accumulated evidence indicates that beta-sheets comprise the basic building blocks of PrP(Sc). Consensus has been reached about the beta-sheet constitution of the N-terminus of PrP, but the constitution of C-terminal beta-sheets is heavily debated. By evaluating the most recent observations regarding the dynamics and structures of PrP, we propose that helix 2 is more likely than helices 1 and 3 to participate in beta-sheet formation. This hypothesis also provides clues to explaining an intriguing phenomenon in prion biology-the lack of PDs in non-mammals.
关于正常朊病毒蛋白（PrP(C)）和瘙痒症异构体（PrP(Sc)）的结构信息对于阐明朊病毒病（PDs）的发病机制至关重要。尽管 PrP(C) 的三维结构已经成功确定，但 PrP(Sc) 的结构细节仍然难以捉摸。然而，大量证据表明β-片层构成了 PrP(Sc)的基本构建块。关于 PrP 的 N 端β-片层组成已经达成共识，但 C 端β-片层的组成仍存在争议。通过评估关于 PrP 动力学和结构的最新观察结果，我们提出螺旋 2比螺旋 1 和 3更有可能参与β-片层形成。这一假设也为解释朊病毒生物学中的一个有趣现象——非哺乳动物中缺乏 PDs 提供了线索。
