Strain-specified relative conformational stability of the scrapie prion protein
Strain-specified relative conformational stability of the scrapie prion protein
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DOI：
10.1110/ps.39201
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发表时间：
2001-04-01
期刊：
影响因子：
8
通讯作者：
Prusiner, SB
中科院分区：
文献类型：
--
作者：
Peretz, D;Scott, MR;Prusiner, SB
对朊病毒生物学和疾病的研究已经阐明了几个新概念，但没有一个比区分不同朊病毒株的生物学特性被赋予致病朊病毒蛋白（PrPSC）的提议更异端。为了探索这一假设，我们研究了PrPSC的属性，从八个朊病毒分离，在叙利亚仓鼠（SHa）繁殖。使用抗蛋白酶消化作为标记的未变性蛋白质，我们研究了这些PrPSC分子的构象稳定性。所有8个分离株显示S形模式的过渡，从本地变性PrPSC作为增加盐酸胍（GdnHCl）浓度的函数。对于Sc237、HY、SHa（Me 7）和MT-CS分离株，半数最大变性发生在平均值为1.48 M GdnHCl时，所有这些分离株都具有类似于75天的孵育期; DY菌株的浓度为1.08 M，潜伏期与170-d相似，SHa（RML）和139 H菌株的浓度为1.25 M，潜伏期与180-d相似。d潜伏期。Me 7-H株的平均浓度为1.39 M盐酸钆，潜伏期约为320 d，根据这些结果，8株朊病毒分离成4个不同的组。我们的研究结果支持非正统的建议，不同的PrPSC构象加密朊病毒株的生物学特性。
Studies of prion biology and diseases have elucidated several new concepts, but none was more heretical than the proposal that the biological properties that distinguish different prion strains are enciphered in the disease-causing prion protein (PrPSC). To explore this postulate, we examined the properties of PrPSC from eight prion isolates that propagate in Syrian hamster (SHa). Using resistance to protease digestion as a marker for the undenatured protein, we examined the conformational stabilities of these PrPSC molecules. All eight isolates showed sigmoidal patterns of transition from native to denatured PrPSC as a function of increasing guanidine hydrochloride (GdnHCl) concentration. Half-maximal denaturation occurred at a mean value of 1.48 M GdnHCl for the Sc237, HY, SHa(Me7), and MT-CS isolates, all of which have similar to 75-d incubation periods; a concentration of 1.08 M was found for the DY strain with a similar to 170-d incubation period and similar to1.25 M for the SHa(RML) and 139H isolates with similar to 180-d incubation periods. A mean value of 1.39 M GdnHCl for the Me7-H strain with a similar to 320-d incubation period was found. Based on these results, the eight prion strains segregated into four distinct groups. Our results support the unorthodox proposal that distinct PrPSC conformers encipher the biological properties of prion strains.