Seeded conversion of recombinant prion protein to a disulfide-bonded oligomer by a reduction-oxidation process
Seeded conversion of recombinant prion protein to a disulfide-bonded oligomer by a reduction-oxidation process
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DOI：
10.1038/nsb961
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发表时间：
2003-09-01
期刊：
影响因子：
--
通讯作者：
Eisenberg, D
中科院分区：
文献类型：
--
作者：
Lee, S;Eisenberg, D
朊病毒蛋白 PrPSc 的传染性形式通过将正常细胞朊病毒蛋白分子 PrPC 转化为另一种 PrPSc 分子来自我繁殖。尚未证明重组朊病毒蛋白可以将朊病毒蛋白分子从PrPC转化为PrPSc。在这里，我们展示了重组仓鼠朊病毒蛋白通过体外氧化还原过程转化为第二种形式 PrPRDX，并且这种 PrPRDX 形式引发了其他 PrPC 分子向 PrPRDX 形式的转化。转化形式显示出 PrPSc 特有的寡聚和晶种转化特性。我们还发现寡聚化可以在体外逆转。 X 射线纤维衍射表明寡聚朊病毒蛋白具有类淀粉样结构。涉及分子间二硫键的结构域交换模型可以解释朊病毒蛋白两种分子形式的稳定性和共存以及第二种形式的自我繁殖能力。
The infectious form of prion protein, PrPSc, self-propagates by its conversion of the normal, cellular prion protein molecule PrPC to another PrPSc molecule. It has not yet been demonstrated that recombinant prion protein can convert prion protein molecules from PrPC to PrPSc. Here we show that recombinant hamster prion protein is converted to a second form, PrPRDX, by a redox process in vitro and that this PrPRDX form seeds the conversion of other PrPC molecules to the PrPRDX form. The converted form shows properties of oligomerization and seeded conversion that are characteristic of PrPSc. We also find that the oligomerization can be reversed in vitro. X-ray fiber diffraction suggests an amyloid-like structure for the oligomerized prion protein. A domain-swapping model involving intermolecular disulfide bonds can account for the stability and coexistence of two molecular forms of prion protein and the capacity of the second form for self-propagation.