Dependence of the Formation of Tau and Aβ Peptide Mixed Aggregates on the Secondary Structure of the N-Terminal Region of Aβ,The Journal of Physical Chemistry B

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Dependence of the Formation of Tau and Aβ Peptide Mixed Aggregates on the Secondary Structure of the N-Terminal Region of Aβ
The Journal of Physical Chemistry B ( IF 2.8 ) Pub Date : 2018-07-10 , DOI: 10.1021/acs.jpcb.8b04647
Ana V. Rojas ₁ , Gia G. Maisuradze ₂ , Harold A. Scheraga ₂

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One of the hallmarks of Alzheimer’s disease is the formation of aggregates of the tau protein, a process that can be facilitated by the presence of fibrils formed by the amyloid β peptide (Aβ). However, the mechanism that triggers tau aggregation is still a matter of debate. The effect of Aβ₄₀ fibrils on the aggregation of the repeat domain of tau (TauRD) is investigated here by employing coarse-grained molecular dynamics simulations. The results indicate that the repeat domain of tau has a high affinity for Aβ₄₀ fibrils, with the ₂₆₁GSTENLK₂₆₇ fragment of tau driving TauRD toward the ₁₆KLVFFA₂₁ fragment in Aβ₄₀. Monomeric Aβ₄₀, in which the ₁₆KLVFFA₂₁ fragment is rarely found in an extended conformation (as in the fibril), has a low affinity for the TauRD, indicating that the ability of Aβ₄₀ fibrils to bind to the TauRD depends on the ₁₆KLVFFA₂₁ fragment of Aβ adopting an extended conformation.

中文翻译：

Tau和Aβ肽混合聚集体的形成对AβN末端区域二级结构的依赖性

阿尔茨海默氏病的标志之一是tau蛋白聚集体的形成，这一过程可通过存在由淀粉样β肽（Aβ）形成的原纤维来促进。但是，触发tau聚集的机制仍是一个争论的问题。Aβ的影响₄₀原纤维上tau的重复结构域（TauRD）的聚合是通过使用粗粒度的分子动力学模拟这里调查。结果表明，tau的重复结构域具有用于Aβ的亲和性高₄₀原纤维，具有₂₆₁ GSTENLK ₂₆₇的tau驱动TauRD朝向的片段₁₆ KLVFFA ₂₁在Aβ片段₄₀。单体_Aβ40，其中在扩展构象中很少发现₁₆ KLVFFA ₂₁片段（如在原纤维中），对TauRD的亲和力低，表明_Aβ40纤维与TauRD结合的能力取决于₁₆ KLVFFA ₂₁片段的Aβ采用扩展构象。

更新日期：2018-07-12

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