Schweers O, Schönbrunn-Hanebeck E, Marx A, Mandelkow E
Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.
J Biol Chem. 1994 Sep 30;269(39):24290-7.
We have studied the conformation of tau protein and Alzheimer paired helical filaments (PHF) by several spectroscopic, scattering, and imaging methods revealing the overall shape and the conformation of the polypeptide backbone. Tau protein behaves in solution as if it were denatured; no evidence for compact folding was detected. The protein is highly extended, there is no defined radius of gyration, and the scattering is best described by that of a random ("Gaussian") polymer. CD and Fourier transform infrared spectroscopy show only a minimal content of ordered secondary structure (alpha-helix or beta-sheet). Similarly, PHFs from Alzheimer brain tissue show no detectable secondary structure by x-ray diffraction or spectroscopy. It is thus unlikely that the aggregation of tau into Alzheimer PHFs is based on interactions between strands of beta-sheets (a model currently favored for other disease-related polymers such as beta-amyloid fibers of Alzheimer's disease).
我们通过多种光谱、散射和成像方法研究了tau蛋白和阿尔茨海默病配对螺旋丝（PHF）的构象，揭示了多肽主链的整体形状和构象。tau蛋白在溶液中的行为就好像它已变性；未检测到紧密折叠的证据。该蛋白高度伸展，没有确定的回转半径，其散射情况最好用随机（“高斯”）聚合物来描述。圆二色光谱和傅里叶变换红外光谱显示有序二级结构（α-螺旋或β-折叠）的含量极少。同样，来自阿尔茨海默病脑组织的PHF通过X射线衍射或光谱法未显示可检测到的二级结构。因此，tau聚集成阿尔茨海默病PHF不太可能是基于β-折叠链之间的相互作用（这是目前其他与疾病相关的聚合物如阿尔茨海默病的β-淀粉样纤维所青睐的模型）。
