Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany and Institute of Biological Information Processing - Structural Biochemistry (IBI-7), Research Centre Jülich, Jülich, Germany.
Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
Chem Commun (Camb). 2021 Jan 28;57(7):947-950. doi: 10.1039/d0cc06607a.
Amyloid β (Aβ) monomers are the smallest assembly units, and play an important role in most of the individual processes involved in amyloid fibril formation. An important question is whether the monomer can adopt transient fibril-like conformations in solution. Here we use enhanced sampling simulations to study the Aβ42 monomer structural flexibility. We show that the monomer frequently adopts conformations with the N-terminus region structured very similarly to the conformation it adopts inside the fibril. This intrinsic propensity of monomeric Aβ to adopt fibril-like conformations could explain the low free energy barrier for Aβ42 fibril elongation.
淀粉样蛋白β (Aβ) 单体是最小的组装单元，在淀粉样纤维形成过程中涉及的大多数单个过程中都起着重要作用。一个重要的问题是单体是否可以在溶液中采用短暂的纤维状构象。在这里，我们使用增强采样模拟来研究 Aβ42 单体的结构灵活性。我们表明，单体经常采用具有非常类似于纤维内构象的 N 端区域结构的构象。单体 Aβ 采用纤维样构象的这种内在倾向可以解释 Aβ42 纤维伸长的低自由能势垒。
