利用新型抗体追踪种间传播过程中异常朊病毒蛋白的构象转变。
Tracing conformational transition of abnormal prion proteins during interspecies transmission by using novel antibodies.
机构信息
Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017, Japan.
出版信息
J Biol Chem. 2010 Apr 16;285(16):11931-6. doi: 10.1074/jbc.M109.058859. Epub 2010 Feb 22.
Abstract
Conformational differences in abnormal prion proteins (PrP(Sc)) have been postulated to produce different prion phenotypes. During the interspecies transmission of prions, the conformation of PrP(Sc) may change with passage; however, little is known about the mechanism of PrP(Sc) transition. In this study, novel PrP(Sc)-specific monoclonal antibodies (mAbs) were developed that could detect the PrP(Sc) of mouse but not that of sheep. By using these mAbs, we attempted to examine PrP(Sc) accumulated in mice inoculated with sheep scrapie serially up to five passages. The presence of PrP(Sc) in the mice was confirmed at all passages; however, mAb-bound PrP(Sc) conformer was detected only from the third passage onward. The generated mAb enabled tracing of a particular conformer during adaptation in sheep-to-mice transmission of prion, suggesting that the conformational transition of PrP(Sc) was caused by propagation of this conformer. Such mAbs capable of discriminating conformational differences may allow us to address questions concerning PrP(Sc) conformation and strain diversity.
摘要
构象差异的异常朊病毒蛋白（PrP（Sc））已被假定产生不同的朊病毒表型。在朊病毒的种间传播过程中，PrP（Sc）的构象可能会随着传递而发生变化；然而，对于 PrP（Sc）转变的机制知之甚少。在这项研究中，开发了新型的 PrP（Sc）特异性单克隆抗体（mAbs），可检测到小鼠的 PrP（Sc），但不能检测到绵羊的 PrP（Sc）。利用这些 mAbs，我们试图检查用绵羊瘙痒病连续传代至五代的小鼠中积累的 PrP（Sc）。在所有传代中均证实了小鼠中存在 PrP（Sc）；然而，仅从第三传代开始才检测到 mAb 结合的 PrP（Sc）构象体。所产生的 mAb 可在绵羊到小鼠的朊病毒传播过程中对特定构象体进行追踪，表明 PrP（Sc）的构象转变是由该构象体的传播引起的。这种能够区分构象差异的 mAb 可能使我们能够解决有关 PrP（Sc）构象和株多样性的问题。
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