Center for Cancer Research Nanobiology Program NCI-Frederick, Frederick, MD 21702, USA.
Biochemistry. 2011 Jun 14;50(23):5172-81. doi: 10.1021/bi200400u. Epub 2011 May 18.
Amyloid plaques and neurofibrillary tangles simultaneously accumulate in Alzheimer's disease (AD). It is known that Aβ and tau exist together in the mitochondria; however, the interactions between Aβ oligomers and tau are controversial. Moreover, it is still unclear which specific domains in the tau protein can interact with Aβ oligomers and what could be the effect of these interactions. Herein, we examine three different Aβ-tau oligomeric complexes. These complexes present interactions of Aβ with three domains in the tau protein; all contain high β-structure propensity in their R2, R3, and R4 repeats. Our results show that, among these, Aβ oligomers are likely to interact with the R2 domain to form a stable complex with better alignment in the turn region and the β-structure domain. We therefore propose that the R2 domain can interact with soluble Aβ oligomers and consequently promote aggregation. EM and AFM images and dimensions revealed highly polymorphic tau aggregates. We suggest that the polymorphic tau and Aβ-tau aggregates may be largely due to repeat sequences which are prone to variable turn locations along the tau repeats.
淀粉样斑块和神经原纤维缠结同时在阿尔茨海默病（AD）中积累。已知 Aβ 和 tau 一起存在于线粒体中；然而，Aβ 寡聚体和 tau 之间的相互作用存在争议。此外，tau 蛋白中哪些特定结构域可以与 Aβ 寡聚体相互作用，以及这些相互作用的影响是什么，目前仍不清楚。在此，我们研究了三种不同的 Aβ-tau 寡聚复合物。这些复合物表现出 Aβ 与 tau 蛋白中三个结构域的相互作用；所有这些都在其 R2、R3 和 R4 重复中表现出高 β-结构倾向。我们的结果表明，在这些复合物中，Aβ 寡聚体可能与 R2 结构域相互作用，形成一个具有更好排列的稳定复合物，在转角区域和 β-结构域。因此，我们提出 R2 结构域可以与可溶性 Aβ 寡聚体相互作用，从而促进聚集。EM 和 AFM 图像和尺寸揭示了高度多态性的 tau 聚集物。我们建议，多态性 tau 和 Aβ-tau 聚集物可能主要是由于重复序列容易沿 tau 重复发生可变的转角位置。
