Tompa P, Friedrich P
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary.
Neuroscience. 1998 Oct;86(4):1037-43. doi: 10.1016/s0306-4522(98)00148-1.
Prions are infectious agents widely implicated in a variety of mammalian neurodegenerative diseases generally referred to as transmissible spongiform encephalopathies. Their infectivity is primarily associated with an aberrant conformation of a host-encoded protein, the prion protein, induced by the prion itself in an autocatalytic reaction. The physiological function of this protein is not known. In this paper we suggest that alternative conformations of the prion protein, other than its pathological scrapie state, exist and that the self-sustaining autocatalytic propagation of these states underlies its normal cellular function. In kinetic model calculations we show that the prion protein may constitute a bi-stable molecular switch that can structurally encode and stably store information. A number of cases of prion involvement in normal cellular function and ample molecular detail of pathological prion propagation are cited and correlated to substantiate the implications of this tenet. Our contention is that the prion hypothesis should be extended to a wide variety of physiological processes. We propose that prion proteins are stable determinants of phenotype, operating in diverse functions possibly including memory.
朊病毒是一种感染性因子，广泛涉及多种哺乳动物神经退行性疾病，通常被称为传染性海绵状脑病。它们的感染性主要与宿主编码蛋白——朊病毒蛋白的异常构象有关，这种构象是由朊病毒自身在自催化反应中诱导产生的。该蛋白的生理功能尚不清楚。在本文中，我们提出，朊病毒蛋白除了其病理性瘙痒病状态外，还存在其他构象，并且这些状态的自我维持自催化传播是其正常细胞功能的基础。在动力学模型计算中，我们表明朊病毒蛋白可能构成一个双稳态分子开关，能够在结构上编码并稳定存储信息。文中引用了许多朊病毒参与正常细胞功能的案例以及病理性朊病毒传播的大量分子细节，并将它们关联起来以证实这一观点的含义。我们的论点是，朊病毒假说应扩展到广泛的生理过程。我们提出，朊病毒蛋白是表型的稳定决定因素，可能在包括记忆在内的多种功能中发挥作用。
