Prusiner S B
Departments of Neurology and of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13363-83. doi: 10.1073/pnas.95.23.13363.
Prions are unprecedented infectious pathogens that cause a group of invariably fatal neurodegenerative diseases by an entirely novel mechanism. Prion diseases may present as genetic, infectious, or sporadic disorders, all of which involve modification of the prion protein (PrP). Bovine spongiform encephalopathy (BSE), scrapie of sheep, and Creutzfeldt-Jakob disease (CJD) of humans are among the most notable prion diseases. Prions are transmissible particles that are devoid of nucleic acid and seem to be composed exclusively of a modified protein (PrPSc). The normal, cellular PrP (PrPC) is converted into PrPSc through a posttranslational process during which it acquires a high beta-sheet content. The species of a particular prion is encoded by the sequence of the chromosomal PrP gene of the mammals in which it last replicated. In contrast to pathogens carrying a nucleic acid genome, prions appear to encipher strain-specific properties in the tertiary structure of PrPSc. Transgenetic studies argue that PrPSc acts as a template upon which PrPC is refolded into a nascent PrPSc molecule through a process facilitated by another protein. Miniprions generated in transgenic mice expressing PrP, in which nearly half of the residues were deleted, exhibit unique biological properties and should facilitate structural studies of PrPSc. While knowledge about prions has profound implications for studies of the structural plasticity of proteins, investigations of prion diseases suggest that new strategies for the prevention and treatment of these disorders may also find application in the more common degenerative diseases.
朊病毒是前所未有的传染性病原体，通过一种全新的机制引发一组 invariably 致命的神经退行性疾病。朊病毒疾病可能表现为遗传性、传染性或散发性疾病，所有这些都涉及朊病毒蛋白（PrP）的修饰。牛海绵状脑病（BSE）、绵羊瘙痒病和人类克雅氏病（CJD）是最著名的朊病毒疾病。朊病毒是可传播的颗粒，不含核酸，似乎仅由一种修饰蛋白（PrPSc）组成。正常的细胞 PrP（PrPC）通过翻译后过程转化为 PrPSc，在此过程中它获得了高β-折叠含量。特定朊病毒的种类由其最后复制的哺乳动物染色体 PrP 基因的序列编码。与携带核酸基因组的病原体不同，朊病毒似乎在 PrPSc 的三级结构中编码了菌株特异性特性。转基因研究表明，PrPSc 作为模板，PrPC 通过另一种蛋白质促进的过程重新折叠成新生的 PrPSc 分子。在表达 PrP 的转基因小鼠中产生的微小朊病毒，其中近一半的残基被删除，表现出独特的生物学特性，应该有助于 PrPSc 的结构研究。虽然关于朊病毒的知识对蛋白质结构可塑性的研究有深远影响，但对朊病毒疾病的研究表明，预防和治疗这些疾病的新策略也可能应用于更常见的退行性疾病。
