Berriman John, Serpell Louise C, Oberg Keith A, Fink Anthony L, Goedert Michel, Crowther R Anthony
Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 2QH, United Kingdom.
Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):9034-8. doi: 10.1073/pnas.1530287100. Epub 2003 Jul 9.
Abnormal filaments consisting of hyperphosphorylated microtubule-associated protein tau form in the brains of patients with Alzheimer's disease, Down's syndrome, and various dementing tauopathies. In Alzheimer's disease and Down's syndrome, the filaments have two characteristic morphologies referred to as paired helical and straight filaments, whereas in tauopathies, there is a wider range of morphologies. There has been controversy in the literature concerning the internal molecular fine structure of these filaments, with arguments for and against the cross-beta structure demonstrated in many other amyloid fibers. The difficulty is to produce from brain pure preparations of filaments for analysis. One approach to avoid the need for a pure preparation is to use selected area electron diffraction from small groups of filaments of defined morphology. Alternatively, it is possible to assemble filaments in vitro from expressed tau protein to produce a homogeneous specimen suitable for analysis by electron diffraction, x-ray diffraction, and Fourier transform infrared spectroscopy. Using both these approaches, we show here that native filaments from brain and filaments assembled in vitro from expressed tau protein have a clear cross-beta structure.
在阿尔茨海默病、唐氏综合征及各种tau蛋白病患者的大脑中，会形成由高度磷酸化的微管相关蛋白tau组成的异常细丝。在阿尔茨海默病和唐氏综合征中，这些细丝有两种特征性形态，即双螺旋丝和直丝，而在tau蛋白病中，形态范围更广。关于这些细丝的内部分子精细结构，文献中存在争议，有人支持也有人反对许多其他淀粉样纤维中显示的交叉β结构。困难在于从大脑中制备用于分析的纯细丝制剂。一种避免需要纯制剂的方法是对确定形态的小群细丝进行选区电子衍射。或者，可以从表达的tau蛋白在体外组装细丝，以产生适合通过电子衍射、X射线衍射和傅里叶变换红外光谱分析的均匀标本。使用这两种方法，我们在此表明，来自大脑的天然细丝和从表达的tau蛋白在体外组装的细丝具有清晰的交叉β结构。
