Prion (PrPSc)-specific epitope defined by a monoclonal antibody
Prion (PrPSc)-specific epitope defined by a monoclonal antibody
复制标题
作者：
Korth, C;Stierli, B;Oesch, B
朊病毒是引起传染性海绵状脑病（TSE）的传染性颗粒。它们至少部分由普遍存在的细胞朊病毒蛋白（PrPC）的同种型（PrPSc）组成。PrPC和PrPSc之间的构象差异从PrPSc中增加的β-折叠含量和蛋白酶抗性中显而易见（参考文献1-3）。在这里，我们描述了一种单克隆抗体，15 B3，可以区分正常和疾病特异性形式的PrP。长期以来一直在寻找这样的抗体，因为它在表征感染性颗粒以及诊断TSE如牛海绵状脑病（BSE）或人类克雅氏病（CJD）方面应该是非常宝贵的。15 B3特异性沉淀牛、鼠或人PrPSc，但不沉淀PrPC，表明它识别来自不同物种的朊病毒共有的表位。利用固定化的合成肽，iue将PrP中的三个多肽片段定位为15 B3表位。在重组小鼠PrP的NMR结构中，15 B3表位的第2和第3段在空间上是近邻，并且第1段位于分子的不同部分。我们讨论了PrPSc特异性表位的模型，该模型确保所有三个15 B3段的紧密空间接近性，无论是通过寡聚形式的朊病毒蛋白的分子间接触还是通过分子内重排。
Prions are infectious particles causing transmissible spongiform encephalopathies (TSEs). They consist, at least in part, of an isoform (PrPSc) of the ubiquitous cellular prion protein (PrPC). Conformational differences between PrPC and PrPSc are evident from increased beta-sheet content and protease resistance in PrPSc (refs 1-3). Here we describe a monoclonal antibody, 15B3, that can discriminate between the normal and disease-specific forms of PrP. Such an antibody has been long sought as it should be invaluable far characterizing the infectious particle as well as for diagnosis of TSEs such as bovine spongiform encephalopathy (BSE) or Creutzfeldt-Jakob disease (CJD) in humans. 15B3 specifically precipitates bovine, murine or human PrPSc, but not PrPC, suggesting that it recognizes an epitope common to prions from different species. Using immobilized synthetic peptides, iue mapped three polypeptide segments in PrP as the 15B3 epitope. In the NMR structure of recombinant mouse PrP, segments 2 and 3 of the 15B3 epitope are near neighbours in space, and segment 1 is located in a different part nf the molecule, We discuss models for the PrPSc-specific epitope that ensure close spatial proximity of all three 15B3 segments, either by intermolecular contacts in oligomeric forms of the prion protein or by intramolecular rearrangement.