Institute for Hygiene, Westfälische Wilhelms-University and University Hospital Münster, Robert Koch-Strasse 41, 48149 Münster, Germany.
Comp Immunol Microbiol Infect Dis. 2013 Dec;36(6):599-605. doi: 10.1016/j.cimid.2013.07.004. Epub 2013 Aug 13.
A feature of transmissible spongiform encephalopathies is the accumulation of infectious prion proteins (PrP(Sc)), which are formed by the conversion of physiological prion proteins (PrP(C)). As PrP(C), which is modified posttranslationally with various types of glycoproteins, serves as the substrates for PrP(Sc) conversion, various PrP(C) subtypes may play a role in the formation of PrP(Sc) and species-specific transmission; the cattle disease BSE is transmissible naturally to humans, but the sheep disease scrapie is not. To reveal new mechanisms modulating prion conversion, we analyzed the PrP(C) profiles by determining the differential PrP(C) protein solubilities in the anionic and nonionic detergents N-lauroylsarcosine, N-octyl-β-D-glucopyranoside, CHAPS and deoxycholic acid. We compared the resulting solubility profiles of human PrP(C) with the solubility profiles of PrP(C) from sheep and cattle. The PrP(C) subtypes were differentially soluble. However, non-glycosylated PrP(C) from cattle and human was found explicitly in the insoluble fraction, while non-glycosylated ovine PrP(C) was detected in the soluble fraction. These findings indicate the existence of low-solubility PrP(C) phenotypes in cattle and humans.
传染性海绵状脑病的一个特征是传染性朊病毒蛋白 (PrP(Sc)) 的积累，它是由生理朊病毒蛋白 (PrP(C)) 的转化形成的。由于 PrP(C) 经翻译后修饰与各种类型的糖蛋白结合，作为 PrP(Sc) 转化的底物，各种 PrP(C) 亚型可能在 PrP(Sc) 的形成和种间特异性传播中发挥作用；牛病 BSE 可自然传播给人类，但羊病瘙痒病不能。为了揭示调节朊病毒转化的新机制，我们通过确定阴离子和非离子去污剂 N-月桂酰肌氨酸、N-辛基-β-D-吡喃葡萄糖苷、CHAPS 和脱氧胆酸中差异 PrP(C) 蛋白溶解度来分析 PrP(C) 谱。我们将人 PrP(C) 的溶解度谱与来自绵羊和牛的 PrP(C) 的溶解度谱进行了比较。PrP(C) 亚型具有不同的溶解度。然而，来自牛和人的非糖基化 PrP(C) 被明确发现存在于不溶性部分，而未糖基化的绵羊 PrP(C) 则存在于可溶性部分。这些发现表明在牛和人中存在低溶解度 PrP(C) 表型。
