Distinct Stability States of Disease-Associated Human Prion Protein Identified by Conformation-Dependent Immunoassay
Distinct Stability States of Disease-Associated Human Prion Protein Identified by Conformation-Dependent Immunoassay
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DOI：
10.1128/jvi.01057-10
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发表时间：
2010-11-01
影响因子：
5.4
通讯作者：
Head, Mark W.
中科院分区：
文献类型：
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作者：
Choi, Young Pyo;Peden, Alexander H.;Head, Mark W.
根据朊病毒假说，人类朊病毒疾病的表型和菌株相关性质被认为存在于构象改变的朊病毒蛋白（PrPSc）的疾病相关同种型的物理化学性质中，PrPSc在患有克雅氏病和相关病症（如Gerstmann-Straussler-Scheinker病）的患者的脑中积累。人类朊病毒疾病的分子菌株分型广泛关注蛋白酶抗性朊病毒蛋白（PrPres）的片段大小和糖基化位点占有率的差异以及朊病毒蛋白基因（PRNP）中存在的突变和多态性。在这里，我们报告的结果，采用一种替代策略，专门解决的构象稳定性的PrPSc和以前已被用于表征动物朊病毒株传播给啮齿动物。结果表明，在人类朊病毒疾病中至少有两种不同的构象稳定状态，这两种状态似乎都与PrPres类型完全相关，如通过片段大小或糖基化、PRNP密码子129状态或PRNP中突变的存在或不存在来判断。这些结果表明，构象稳定性代表了一个潜在的表型相关的性质，PrPSc在人类朊病毒疾病的完整描述的进一步的层面。
The phenotypic and strain-related properties of human prion diseases are, according to the prion hypothesis, proposed to reside in the physicochemical properties of the conformationally altered, disease-associated isoform of the prion protein (PrPSc), which accumulates in the brains of patients suffering from Creutzfeldt-Jakob disease and related conditions, such as Gerstmann-Straussler-Scheinker disease. Molecular strain typing of human prion diseases has focused extensively on differences in the fragment size and glycosylation site occupancy of the protease-resistant prion protein (PrPres) in conjunction with the presence of mutations and polymorphisms in the prion protein gene (PRNP). Here we report the results of employing an alternative strategy that specifically addresses the conformational stability of PrPSc and that has been used previously to characterize animal prion strains transmitted to rodents. The results show that there are at least two distinct conformation stability states in human prion diseases, neither of which appears to correlate fully with the PrPres type, as judged by fragment size or glycosylation, the PRNP codon 129 status, or the presence or absence of mutations in PRNP. These results suggest that conformational stability represents a further dimension to a complete description of potentially phenotype-related properties of PrPSc in human prion diseases.