The prion protein, PrP, can adopt at least 2 conformations, the overwhelmingly prevalent cellular conformation (PrP^C) and the scrapie conformation (PrP^Sc). PrP^C features a globular C-terminal domain containing 3 α-helices and a short β-sheet and a long flexible N-terminal tail whose exact conformation in vivo is not yet known and a metastable subdomain with β-strand propensity has been identified within it. The PrP^Sc conformation is very rare and has the characteristics of an amyloid. Furthermore, PrP^Sc is a prion, i.e., it is infectious. This involves 2 steps: (1) PrP^Sc can template PrP^C and coerce it to adopt the PrP^Sc conformation and (2) PrP^Sc can be transmitted between individuals, by oral, parenteral, and other routes and thus propagate as an infectious agent. However, this is a simplification: On the one hand, PrP^Sc is not a single conformation, but rather, a set of alternative similar but distinct conformations. Furthermore, other amyloid conformations of PrP exist with different biochemical and propagative properties. In this issue of PLOS Biology, Asante and colleagues describe the first murine model of familial human prion disease and demonstrate the emergence and propagation of 2 PrP amyloid conformers. Of these, one causes neurodegeneration, whereas the other does not. With its many conformers, PrP is a truly protean protein.

ion病毒蛋白PrP可以采用至少2种构象，即绝大多数细胞构象（PrP ^C）和瘙痒病构象（PrP ^Sc）。PrP ^C具有一个球形的C末端结构域，该结构域包含3个α螺旋和一个短的β-折叠以及一个长的柔性N末端尾巴，其确切的体内构象尚不清楚，并且在其中已鉴定出具有β链倾向的亚稳态亚结构域它。PrP ^Sc构象非常罕见，具有淀粉样蛋白的特征。此外，PrP ^Sc是a病毒，即具有传染性。这涉及两个步骤：（1）PrP ^Sc可以模板化PrP ^C并强制其采用PrP ^Sc构象和（2）PrP ^Sc可以通过口服，肠胃外和其他途径在个体之间传播，因此可以作为传染因子传播。但是，这只是一个简化：一方面，PrP ^Sc不是单个构象，而是一组替代的相似但截然不同的构象。此外，存在其他具有不同生化和繁殖特性的PrP淀粉样蛋白构象。在本期《PLOS生物学》中，Asante及其同事描述了家族性人类病毒疾病的第一个小鼠模型，并证明了2种PrP淀粉样蛋白构象体的出现和繁殖。其中一种引起神经变性，而另一种则不引起。PrP具有许多构象，是一种真正的蛋白质蛋白。