State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300353, China.
Biodesign Center, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
Angew Chem Int Ed Engl. 2018 May 4;57(19):5418-5422. doi: 10.1002/anie.201801498. Epub 2018 Mar 26.
Reconfiguration of membrane protein channels for gated transport is highly regulated under physiological conditions. However, a mechanistic understanding of such channels remains challenging owing to the difficulty in probing subtle gating-associated structural changes. Herein, we show that charge neutralization can drive the shape reconfiguration of a biomimetic 6-helix bundle DNA nanotube (6HB). Specifically, 6HB adopts a compact state when its charge is neutralized by Mg ; whereas Na switches it to the expanded state, as revealed by MD simulations, small-angle X-ray scattering (SAXS), and FRET characterization. Furthermore, partial neutralization of the DNA backbone charges by chemical modification renders 6HB compact and insensitive to ions, suggesting an interplay between electrostatic and hydrophobic forces in the channels. This system provides a platform for understanding the structure-function relationship of biological channels and designing rules for the shape control of DNA nanostructures in biomedical applications.
在生理条件下，膜蛋白通道的门控运输的重排受到高度调控。然而，由于探测细微的门控相关结构变化具有挑战性，因此对这种通道的机制理解仍然具有挑战性。本文中，我们展示了电荷中和可以驱动仿生 6 螺旋束 DNA 纳米管（6HB）的形状重排。具体而言，当 6HB 的电荷被 Mg 中和时，其采用紧凑状态；而 Na 将其切换到扩展状态，这通过 MD 模拟、小角 X 射线散射（SAXS）和 FRET 特性揭示。此外，通过化学修饰部分中和 DNA 骨架电荷，使得 6HB 紧凑且对离子不敏感，这表明在通道中静电和疏水相互作用之间存在相互作用。该系统为理解生物通道的结构-功能关系以及在生物医学应用中设计 DNA 纳米结构的形状控制规则提供了一个平台。
