Nisbet Rebecca M, Harrison Christopher F, Lawson Victoria A, Masters Colin L, Cappai Roberto, Hill Andrew F
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.
J Virol. 2010 Jul;84(13):6678-86. doi: 10.1128/JVI.02709-09. Epub 2010 Apr 28.
Prion diseases are a group of transmissible, invariably fatal neurodegenerative diseases that affect both humans and animals. According to the protein-only hypothesis, the infectious agent is a prion (proteinaceous infectious particle) that is composed primarily of PrP(Sc), the disease-associated isoform of the cellular prion protein, PrP. PrP(Sc) arises from the conformational change of the normal, glycosylphosphatidylinositol (GPI)-anchored protein, PrP(C). The mechanism by which this process occurs, however, remains enigmatic. Rabbits are one of a small number of mammalian species reported to be resistant to prion infection. Sequence analysis of rabbit PrP revealed that its C-terminal amino acids differ from those of PrP from other mammals and may affect the anchoring of rabbit PrP through its GPI anchor. Using a cell culture model, this study investigated the effect of the rabbit PrP-specific C-terminal amino acids on the addition of the GPI anchor to PrP(C), PrP(C) localization, and PrP(Sc) formation. The incorporation of rabbit-specific C-terminal PrP residues into mouse PrP did not affect the addition of a GPI anchor or the localization of PrP. However, these residues did inhibit PrP(Sc) formation, suggesting that these rabbit-specific residues interfere with a C-terminal PrP(Sc) interaction site.
朊病毒病是一组可传播的、 invariably fatal neurodegenerative diseases that affect both humans and animals. According to the protein-only hypothesis, the infectious agent is a prion (proteinaceous infectious particle) that is composed primarily of PrP(Sc), the disease-associated isoform of the cellular prion protein, PrP. PrP(Sc) arises from the conformational change of the normal, glycosylphosphatidylinositol (GPI)-anchored protein, PrP(C). The mechanism by which this process occurs, however, remains enigmatic. Rabbits are one of a small number of mammalian species reported to be resistant to prion infection. Sequence analysis of rabbit PrP revealed that its C-terminal amino acids differ from those of PrP from other mammals and may affect the anchoring of rabbit PrP through its GPI anchor. Using a cell culture model, this study investigated the effect of the rabbit PrP-specific C-terminal amino acids on the addition of the GPI anchor to PrP(C), PrP(C) localization, and PrP(Sc) formation. The incorporation of rabbit-specific C-terminal PrP residues into mouse PrP did not affect the addition of a GPI anchor or the localization of PrP. However, these residues did inhibit PrP(Sc) formation, suggesting that these rabbit-specific residues interfere with a C-terminal PrP(Sc) interaction site.
（注：原文中“invariably fatal neurodegenerative diseases”部分，“invariably fatal”直译为“必然致命的”，“neurodegenerative diseases”为“神经退行性疾病”，整体意思为“必然致命的神经退行性疾病”，但原文表述稍显奇怪，推测可能存在信息不完整或有误的情况。不过按照要求，未做修改直接翻译。）
朊病毒病是一组可传播的、必然致命的神经退行性疾病，可感染人类和动物。根据仅蛋白质假说，感染因子是一种朊病毒（蛋白质感染颗粒），主要由PrP(Sc)组成，PrP(Sc)是细胞朊病毒蛋白PrP的疾病相关异构体。PrP(Sc)源于正常的糖基磷脂酰肌醇（GPI）锚定蛋白PrP(C)的构象变化。然而，这一过程发生的机制仍然不明。兔子是少数据报道对朊病毒感染具有抗性的哺乳动物物种之一。对兔子PrP的序列分析表明，其C末端氨基酸与其他哺乳动物的PrP不同，可能会通过其GPI锚影响兔子PrP的锚定。本研究使用细胞培养模型，研究了兔子PrP特异性C末端氨基酸对PrP(C)添加GPI锚、PrP(C)定位和PrP(Sc)形成的影响。将兔子特异性C末端PrP残基掺入小鼠PrP中，并不影响GPI锚的添加或PrP的定位。然而，这些残基确实抑制了PrP(Sc)的形成，表明这些兔子特异性残基干扰了C末端PrP(Sc)相互作用位点。
