Mandelkow E M, Biernat J, Drewes G, Steiner B, Lichtenberg-Kraag B, Wille H, Gustke N, Mandelkow E
Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.
Ann N Y Acad Sci. 1993 Sep 24;695:209-16. doi: 10.1111/j.1749-6632.1993.tb23054.x.
This paper summarizes our recent studies on microtubule-associated protein tau and its pathological state resembling that of the paired helical filaments of Alzheimer's disease. The Alzheimer-like state of tau protein can be identified and analyzed in terms of certain phosphorylation sites and phosphorylation-dependent antibody epitopes. It can be induced by protein kinases which tend to phosphorylate serine or threonine residues followed by a proline; this includes mitogen-activated protein kinase (MAPK) and glycogen-synthase kinase 3 (GSK-3). Both of these are tightly associated with microtubules as well as with paired helical filaments. Structurally, tau appears as a rod-like molecule; it tends to self-associate into dimers whose monomers are antiparallel. Constructs of truncated tau made up of antiparallel dimers of the microtubule binding domain can be assembled into paired helical filaments in vitro.
本文总结了我们最近关于微管相关蛋白tau及其类似阿尔茨海默病双螺旋丝病理状态的研究。tau蛋白的阿尔茨海默样状态可根据某些磷酸化位点和磷酸化依赖性抗体表位来识别和分析。它可由倾向于磷酸化丝氨酸或苏氨酸残基且其后紧跟脯氨酸的蛋白激酶诱导产生；这包括丝裂原活化蛋白激酶（MAPK）和糖原合酶激酶3（GSK-3）。这两种激酶都与微管以及双螺旋丝紧密相关。从结构上看，tau呈现为杆状分子；它倾向于自缔合形成二聚体，其单体呈反平行排列。由微管结合域的反平行二聚体组成的截短tau构建体可在体外组装成双螺旋丝。
