Propagation of transmissible spongiform encephalopathies involves the conversion of cellular prion protein, PrP^C, into a misfolded oligomeric form, PrP^Sc. The most common hereditary prion disease is a genetic form of Creutzfeldt-Jakob disease in humans, in which a mutation in the prion gene results in a glutamic acid to lysine substitution at position 200 (E200K) in PrP. In cattle, the analogous amino acid substitution is found at residue 211 (E211K) and has been associated with a case of bovine spongiform encephalopathy. Here, we have compared the secondary structure of E211K to that of wild type using circular dichroism and completed a thermodynamic analysis of the folding of recombinant wild type and E211K variants of the bovine prion protein. The secondary structure of the E211K variant was essentially indistinguishable from that of wild type. The thermodynamic stability of E211K substitution showed a slight destabilization relative to the wild type consistent with results reported for recombinant human prion protein and its mutant E200K. In addition, the E211K variant exhibits a similarly compact denatured state to that of wild type based upon similar m-value and change in heat capacity of unfolding for the proteins. Together these results indicate that residual structure in the denatured state of bPrP is present in both the wild type protein and BSE associated variant E211K. Given this observation, as well as folding similarities reported for other disease associated variants of PrP it is worth consideration that functional aspects of PrP conformation may play a role in the misfolding process.

传播性海绵状脑病的传播涉及将细胞病毒蛋白PrP ^C转化为错误折叠的寡聚形式PrP ^Sc。最常见的遗传性病毒疾病是人类Creutzfeldt-Jakob疾病的一种遗传形式，其中ion病毒基因的突变导致PrP中200位（E200K）处的谷氨酸被赖氨酸取代。在牛中，类似的氨基酸取代存在于残基211（E211K）处，并与一例牛海绵状脑病有关。在这里，我们使用圆二色性比较了E211K与野生型的二级结构，并完成了重组野生型和pr病毒蛋白E211K变体折叠的热力学分析。E211K变体的二级结构与野生型基本上没有区别。相对于野生型，E211K取代的热力学稳定性显示出轻微的不稳定，这与重组人病毒蛋白及其突变体E200K报道的结果一致。另外，基于相似的m值和蛋白质展开的热容量的变化，E211K变体表现出与野生型相似的致密变性状态。这些结果共同表明，野生型蛋白和BSE相关变体E211K中都存在bPrP变性状态的残留结构。鉴于这一观察结果，以及与其他疾病相关的PrP变异报道的折叠相似性，值得考虑的是PrP构象的功能方面可能在错误折叠过程中起作用。E211K变体基于相似的m值和蛋白质展开的热容变化，表现出与野生型相似的致密变性状态。这些结果共同表明，野生型蛋白和BSE相关变体E211K中都存在bPrP变性状态的残留结构。鉴于这一观察结果，以及与其他疾病相关的PrP变异报道的折叠相似性，值得考虑的是PrP构象的功能方面可能在错误折叠过程中起作用。E211K变体基于相似的m值和蛋白质展开的热容变化，表现出与野生型相似的致密变性状态。这些结果共同表明，野生型蛋白和BSE相关变体E211K中都存在bPrP变性状态的残留结构。鉴于此观察结果，以及与其他疾病相关的PrP变异体报道的折叠相似性，值得考虑的是PrP构象的功能方面可能在错误折叠过程中起作用。