Supattapone S, Bouzamondo E, Ball H L, Wille H, Nguyen H O, Cohen F E, DeArmond S J, Prusiner S B, Scott M
Institute for Neurodegenerative Diseases, University of California at San Francisco, San Francisco, California 94143, USA.
Mol Cell Biol. 2001 Apr;21(7):2608-16. doi: 10.1128/MCB.21.7.2608-2616.2001.
An abridged prion protein (PrP) molecule of 106 amino acids, designated PrP106, is capable of forming infectious miniprions in transgenic mice (S. Supattapone, P. Bosque, T. Muramoto, H. Wille, C. Aagaard, D. Peretz, H.-O. B. Nguyen, C. Heinrich, M. Torchia, J. Safar, F. E. Cohen, S. J. DeArmond, S. B. Prusiner, and M. Scott, Cell 96:869-878, 1999). We removed additional sequences from PrP106 and identified a 61-residue peptide, designated PrP61, that spontaneously adopted a protease-resistant conformation in neuroblastoma cells. Synthetic PrP61 bearing a carboxy-terminal lipid moiety polymerized into protease-resistant, beta-sheet-enriched amyloid fibrils at a physiological salt concentration. Transgenic mice expressing low levels of PrP61 died spontaneously with ataxia. Neuropathological examination revealed accumulation of protease-resistant PrP61 within neuronal dendrites and cell bodies, apparently causing apoptosis. PrP61 may be a useful model for deciphering the mechanism by which PrP molecules acquire protease resistance and become neurotoxic.
一种由106个氨基酸组成的截短型朊病毒蛋白（PrP）分子，命名为PrP106，能够在转基因小鼠中形成传染性微小朊病毒（S. 苏帕塔蓬、P. 博斯克、T. 村本、H. 维勒、C. 阿加德、D. 佩雷茨、H.-O. B. 阮、C. 海因里希、M. 托尔基亚、J. 萨法尔、F. E. 科恩、S. J. 迪阿尔蒙德、S. B. 普鲁辛纳和M. 斯科特，《细胞》96:869 - 878，1999年）。我们从PrP106中去除了更多序列，并鉴定出一种61个残基的肽，命名为PrP61，它在神经母细胞瘤细胞中自发形成了抗蛋白酶的构象。带有羧基末端脂质部分的合成PrP61在生理盐浓度下聚合成抗蛋白酶的、富含β-折叠的淀粉样纤维。表达低水平PrP61的转基因小鼠会因共济失调而自发死亡。神经病理学检查显示，抗蛋白酶的PrP61在神经元树突和细胞体内积累，显然导致了细胞凋亡。PrP61可能是一个有用的模型，用于解读PrP分子获得抗蛋白酶能力并变得具有神经毒性的机制。
