THE MAJOR POLYPEPTIDE OF SCRAPIE-ASSOCIATED FIBRILS (SAF) HAS THE SAME SIZE, CHARGE-DISTRIBUTION AND N-TERMINAL PROTEIN-SEQUENCE AS PREDICTED FOR THE NORMAL BRAIN PROTEIN (PRP)
THE MAJOR POLYPEPTIDE OF SCRAPIE-ASSOCIATED FIBRILS (SAF) HAS THE SAME SIZE, CHARGE-DISTRIBUTION AND N-TERMINAL PROTEIN-SEQUENCE AS PREDICTED FOR THE NORMAL BRAIN PROTEIN (PRP)
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DOI：
10.1002/j.1460-2075.1986.tb04539.x
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发表时间：
1986-10-01
期刊：
影响因子：
11.4
通讯作者：
KIMBERLIN, RH
中科院分区：
文献类型：
--
作者：
HOPE, J;MORTON, LJD;KIMBERLIN, RH
瘙痒病相关原纤维 (SAF) 是非常规缓慢感染组的独特结构特征，其中包括瘙痒病和克雅氏病。仓鼠原纤维的主要成分已被描述为具有表观摩尔数的蛋白酶抗性糖蛋白。重量为27,000-30,000 (PrP27-30)。然而，我们在此报告，如果通过旨在最大限度地减少蛋白水解的程序制备原纤维，则与仓鼠 SAF 共纯化的 PrP 蛋白具有 mol。重量为 33,000-35,000 (PrP33-35) 和 26,000-29,000 (PrP26-29)。我们在这些 SAF 蛋白的氨基末端发现了一个 Lys-Lys-Arg-Pro-Lys 序列，该序列在 PrP27-30 中不存在，并且最近被预测为未感染大脑的天然 PrP 蛋白的 N 端序列。主要 SAF 蛋白 (PrP33-35) 及其正常脑同源物具有相同的表观摩尔数。通过二维凝胶分析、银染和免疫印迹分析重量和离子电荷分布。这些结果支持我们的观点，即 PrP33-35 和正常脑 PrP 蛋白可能具有相同的共价结构，并且 PrP 蛋白被募集到这些淀粉样蛋白样 SAF 中，或通过由瘙痒病感染直接或间接引发的不可逆事件与 SAF 的非蛋白成分结合。
Scrapie-associated fibrils (SAF) are unique structures characteristic of the group of unconventional slow infections which includes scrapie and Creutzfeldt-Jakob disease. A major component of hamster fibrils has been described as a protease-resistant glycoprotein with an apparent mol. wt of 27,000-30,000 (PrP27-30). However, we report here that if fibrils are prepared by procedures designed to minimise proteolysis the PrP proteins co-purifying with hamster SAF have mol. wts of 33,000-35,000 (PrP33-35) and 26,000-29,000 (PrP26-29). We find a Lys-Lys-Arg-Pro-Lys sequence at the amino terminus of these SAF proteins, that is absent from PrP27-30, and which has recently been predicted to be the N-terminal sequence of the native PrP protein of uninfected brain. The major SAF protein (PrP33-35) and its normal brain homologue are shown to have the same apparent mol. wt and ionic charge distribution by two-dimensional gel analysis, silver staining and immunoblotting. These results support our view that PrP33-35 and the normal brain PrP protein may have the same covalent structure, and that the PrP protein is recruited into these amyloid-like SAF or into association with a non-protein component of SAF by an irreversible event initiated directly or indirectly by scrapie infection.