Ji Wei, Yuan Chengqian, Chakraborty Priyadarshi, Gilead Sharon, Yan Xuehai, Gazit Ehud
George S. Wise Faculty of Life Sciences, Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv 6997801, Israel.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
Commun Chem. 2019 Jun 13;2(1). doi: 10.1038/s42004-019-0170-z.
Conformational transitions of secondary structures are a crucial factor in many protein misfolding diseases. However, the actual transition of folded proteins into β-sheet-rich structures is not fully understood. Inhibition of aggregate formation, mediated by the β-sheet conformation, and control of the secondary structural transition of proteins and peptides could potentially attenuate the development of amyloid-associated diseases. Here we describe a stoichiometry-controlled secondary structure transition of amyloid-derived dipeptide assemblies from a β-sheet to supramolecular helix conformation through coassembly with a bipyridine derivative. The transition is mainly mediated by the intermolecular hydrogen bonds and π-π interactions between the two components, which induce the altered stacking and conformation of the co-assemblies, as confirmed by experimental results and computational simulations. This work not only exemplifies a feasible strategy to disrupt the β-sheet conformation, underlying amyloid-like fibril formation, but also provides a conceptual basis for the future utilization of the helical nanostructures in various biological applications.
二级结构的构象转变是许多蛋白质错误折叠疾病中的关键因素。然而，折叠蛋白向富含β-折叠结构的实际转变尚未完全明确。由β-折叠构象介导的聚集体形成的抑制以及蛋白质和肽二级结构转变的控制，可能会减缓淀粉样蛋白相关疾病的发展。在此，我们描述了一种化学计量控制的淀粉样二肽组装体二级结构转变，即通过与联吡啶衍生物共组装，从β-折叠转变为超分子螺旋构象。该转变主要由两种组分之间的分子间氢键和π-π相互作用介导，这些相互作用诱导了共组装体堆积和构象的改变，实验结果和计算模拟均证实了这一点。这项工作不仅例证了一种破坏类淀粉样纤维形成所依赖的β-折叠构象的可行策略，还为未来在各种生物应用中利用螺旋纳米结构提供了概念基础。
