Wischik C M, Novak M, Edwards P C, Klug A, Tichelaar W, Crowther R A
Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Proc Natl Acad Sci U S A. 1988 Jul;85(13):4884-8. doi: 10.1073/pnas.85.13.4884.
The paired helical filament, the principal constituent of the neurofibrillary tangles characteristic of Alzheimer disease, is shown to consist of two structurally distinct parts. An external fuzzy region can be removed by Pronase treatment to leave a Pronase-resistant morphologically recognizable core. Scanning transmission electron microscopy gives an estimate for the mass per unit length as 79 kDa.nm-1 before Pronase treatment and 65 kDa.nm-1 after treatment. The fuzzy region carries all the epitopes recognized by two different antisera against microtubule-associated protein tau. By contrast, a monoclonal antibody (mAb) we have raised to paired helical filament cores (mAb 423) decorates Pronase-treated filaments much more strongly than it does untreated ones. We have shown in previous papers that the epitope recognized by mAb 423 is carried by a central 9.5-kDa fragment of tau protein, which therefore forms part of the Pronase-resistant core structure. The remainder of the tau protein incorporated into the filaments must contribute part, if not all, of the fuzzy region. The mass per unit length measurements imply that the three-domain structural subunit of the core that we visualized previously by image reconstruction has a molecular mass of approximately equal to 100 kDa.
成对螺旋丝是阿尔茨海默病特征性神经原纤维缠结的主要成分，它由两个结构不同的部分组成。经链霉蛋白酶处理可去除外部模糊区域，留下链霉蛋白酶抗性的、形态上可识别的核心。扫描透射电子显微镜测定，链霉蛋白酶处理前每单位长度的质量为79 kDa·nm-1，处理后为65 kDa·nm-1。模糊区域带有两种针对微管相关蛋白tau的不同抗血清所识别的所有表位。相比之下，我们制备的一种针对成对螺旋丝核心的单克隆抗体（mAb 423）对经链霉蛋白酶处理的丝的标记要强于未处理的丝。我们在以前的论文中表明，mAb 423识别的表位由tau蛋白的一个9.5 kDa的中央片段携带，因此该片段构成了链霉蛋白酶抗性核心结构的一部分。纳入丝中的tau蛋白的其余部分必定构成了模糊区域的部分（如果不是全部）。每单位长度质量的测量结果表明，我们之前通过图像重建可视化的核心的三结构域结构亚基的分子量约为100 kDa。
