Pérez M, Valpuesta J M, Medina M, Montejo de Garcini E, Avila J
Centro de Biología Molecular Severo Ochoa, (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
J Neurochem. 1996 Sep;67(3):1183-90. doi: 10.1046/j.1471-4159.1996.67031183.x.
Paired helical filaments isolated from the brains of patients with Alzheimer's disease are composed of a major protein component, the microtubule-associated protein termed tau, together with other nonprotein components, including heparan, a glycosaminoglycan, the more extensively sulfated form of which is heparin. As some of these nonprotein components may modulate the assembly of tau into filamentous structures, we have analyzed the ability of the whole tau protein or some of its fragments to self-assemble in the presence of heparin. Different tau fragments, all of them containing some sequences of the tubulin-binding motif, can assemble in vitro into filaments. We have also found formation of polymers with the 18-residue-long peptide corresponding to the third tubulin-binding motif of tau. This suggests that the ability of tau for self-assembly could be localized in a short sequence of amino acids present in the tubulin-binding repeats of the tau molecule.
从阿尔茨海默病患者大脑中分离出的成对螺旋丝由一种主要蛋白质成分——称为tau的微管相关蛋白，以及其他非蛋白质成分组成，包括硫酸乙酰肝素（一种糖胺聚糖，其硫酸化程度更高的形式是肝素）。由于这些非蛋白质成分中的一些可能会调节tau组装成丝状结构的过程，我们分析了完整的tau蛋白或其一些片段在肝素存在下自我组装的能力。不同的tau片段，均包含微管蛋白结合基序的一些序列，能够在体外组装成细丝。我们还发现，与tau的第三个微管蛋白结合基序对应的18个残基长的肽形成了聚合物。这表明tau的自我组装能力可能定位于tau分子微管蛋白结合重复序列中存在的一段短氨基酸序列。
