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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Species specificity in the cell-free conversion of prion protein to protease-resistant forms: a model for the scrapie species barrier.
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Species specificity in the cell-free conversion of prion protein to protease-resistant forms: a model for the scrapie species barrier.

机译：病毒蛋白无细胞转化为蛋白酶抗性形式的物种特异性：痒病物种屏障的模型。

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摘要

Scrapie is a transmissible neurodegenerative disease that appears to result from an accumulation in the brain of an abnormal protease-resistant isoform of prion protein (PrP) called PrPsc. Conversion of the normal, protease-sensitive form of PrP (PrPc) to protease-resistant forms like PrPsc has been demonstrated in a cell-free reaction composed largely of hamster PrPc and PrPsc. We now report studies of the species specificity of this cell-free reaction using mouse, hamster, and chimeric PrP molecules. Combinations of hamster PrPc with hamster PrPsc and mouse PrPc with mouse PrPsc resulted in the conversion of PrPc to protease-resistant forms. Protease-resistant PrP species were also generated in the nonhomologous reaction of hamster PrPc with mouse PrPsc, but little conversion was observed in the reciprocal reaction. Glycosylation of the PrPc precursors was not required for species specificity in the conversion reaction. The relative conversion efficiencies correlated with the relative transmissibilities of these strains of scrapie between mice and hamsters. Conversion experiments performed with chimeric mouse/hamster PrPc precursors indicated that differences between PrPc and PrPsc at residues 139, 155, and 170 affected the conversion efficiency and the size of the resultant protease-resistant PrP species. We conclude that there is species specificity in the cell-free interactions that lead to the conversion of PrPc to protease-resistant forms. This specificity may be the molecular basis for the barriers to interspecies transmission of scrapie and other transmissible spongiform encephalopathies in vivo.
机译：瘙痒病是一种可传播的神经退行性疾病，似乎是由于大脑中积累有一种称为PrPsc的蛋白（PrP）的蛋白酶抗性异常同工型引起的。在主要由仓鼠PrPc和PrPsc组成的无细胞反应中，已证明正常的，对蛋白酶敏感的PrP（PrPc）形式向蛋白酶抗性形式的转化，如PrPsc。现在，我们报告使用鼠标，仓鼠和嵌合PrP分子对该无细胞反应进行物种特异性研究。仓鼠PrPc与仓鼠PrPsc的组合以及小鼠PrPc与小鼠PrPsc的组合导致PrPc转化为蛋白酶抗性形式。在仓鼠PrPc与小鼠PrPsc的非同源反应中也产生了耐蛋白酶的PrP种类，但在相互反应中观察到很少的转化。 PrPc前体的糖基化不需要转化反应中的物种特异性。相对转化效率与这些瘙痒病菌株在小鼠和仓鼠之间的相对透射率相关。用嵌合小鼠/仓鼠PrPc前体进行的转化实验表明，PrPc和PrPsc之间残基139、155和170的差异影响了转化效率和所得蛋白酶抗性PrP物种的大小。我们得出结论，在无细胞相互作用中存在物种特异性，导致PrPc转化为蛋白酶抗性形式。这种特异性可能是体内瘙痒病和其他可传播海绵状脑病种间传播障碍的分子基础。

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