Martins V R
Fundação Antônio Prudente, São Paulo, Brasil.
Braz J Med Biol Res. 1999 Jul;32(7):853-9. doi: 10.1590/s0100-879x1999000700009.
Prions are an unconventional form of infectious agents composed only of protein and involved in transmissible spongiform encephalopathies in humans and animals. The infectious particle is composed by PrPsc which is an isoform of a normal cellular glycosyl-phosphatidylinositol (GPI) anchored protein, PrPc, of unknown function. The two proteins differ only in conformation, PrPc is composed of 40% alpha helix while PrPsc has 60% beta-sheet and 20% alpha helix structure. The infection mechanism is trigged by interaction of PrPsc with cellular prion protein causing conversion of the latter's conformation. Therefore, the infection spreads because new PrPsc molecules are generated exponentially from the normal PrPc. The accumulation of insoluble PrPsc is probably one of the events that lead to neuronal death. Conflicting data in the literature showed that PrPc internalization is mediated either by clathrin-coated pits or by caveolae-like membranous domains. However, both pathways seem to require a third protein (a receptor or a prion-binding protein) either to make the connection between the GPI-anchored molecule to clathrin or to convert PrPc into PrPsc. We have recently characterized a 66-kDa membrane receptor which binds PrPc in vitro and in vivo and mediates the neurotoxicity of a human prion peptide. Therefore, the receptor should have a role in the pathogenesis of prion-related diseases and in the normal cellular process. Further work is necessary to clarify the events triggered by the association of PrPc/PrPsc with the receptor.
朊病毒是一种非常规形式的感染因子，仅由蛋白质组成，与人类和动物的传染性海绵状脑病有关。感染性颗粒由PrPsc组成，它是一种正常细胞糖基磷脂酰肌醇（GPI）锚定蛋白PrPc的异构体，其功能未知。这两种蛋白质仅在构象上有所不同，PrPc由40%的α螺旋组成，而PrPsc具有60%的β折叠和20%的α螺旋结构。感染机制是由PrPsc与细胞朊病毒蛋白的相互作用触发的，导致后者构象的转变。因此，感染得以传播，因为新的PrPsc分子从正常的PrPc中呈指数级产生。不溶性PrPsc的积累可能是导致神经元死亡的事件之一。文献中的矛盾数据表明，PrPc的内化是由网格蛋白包被小窝或类窖膜结构域介导的。然而，这两条途径似乎都需要第三种蛋白质（一种受体或朊病毒结合蛋白），要么在GPI锚定分子与网格蛋白之间建立联系，要么将PrPc转化为PrPsc。我们最近鉴定了一种66 kDa的膜受体，它在体外和体内都能结合PrPc，并介导一种人类朊病毒肽的神经毒性。因此，该受体应该在朊病毒相关疾病的发病机制和正常细胞过程中发挥作用。需要进一步的研究来阐明PrPc/PrPsc与受体结合所引发的事件。
