基于互相关分析来解析 flavonoids 对 mitoBK 通道构象动力学的调节作用。
The cross-correlation-based analysis to digest the conformational dynamics of the mitoBK channels in terms of their modulation by flavonoids.
机构信息
Department of Physical Chemistry and Technology of Polymers, Silesian University of Technology, Strzody 9, Gliwice, 44-100, Poland.
Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1A, Chorzów, 41-500, Poland.
出版信息
Eur Biophys J. 2023 Oct;52(6-7):569-582. doi: 10.1007/s00249-023-01666-9. Epub 2023 Jun 30.
The activity of mitochondrial large-conductance voltage- and [Formula: see text]-activated [Formula: see text] channels (mitoBK) is regulated by a number of biochemical factors, including flavonoids. In particular, naringenin (Nar) and quercetin (Que) reached reasonable scientific attention due to their well-pronounced channel-activating effects. The open-reinforcing outcomes of Nar and Que on the mitoBK channel gating have been already reported. Nevertheless, the molecular picture of the corresponding channel-ligand interactions remains still to be revealed. In this work, we investigate the effects of the Nar and Que on the conformational dynamics of the mitoBK channel. In this aim, the cross-correlation-based analysis of the single-channel signals recorded by the patch-clamp method is performed. The obtained results in the form of phase space diagrams enable us to visually monitor the effects exerted by the considered flavonoids at the level of temporal characteristics of repetitive sequences of channel conformations. It turns out that the mitoBK channel activation by naringenin and quercetin does not lead to the change in the number of clusters within the phase space diagrams, which can be related to the constant number of available channel macroconformations regardless of the flavonoid administration. The localization and occupancy of the clusters of cross-correlated sequences suggest that mitoBK channel stimulation by flavonoids affects the relative stability of channel conformations and the kinetics of switching between them. For most clusters, greater net effects are observed in terms of quercetin administration in comparison with naringenin. It indicates stronger channel interaction with Que than Nar.
线粒体大电导电压和钙激活钾通道(mitoBK)的活性受许多生化因素的调节,包括类黄酮。特别是,柚皮素(Nar)和槲皮素(Que)由于其明显的通道激活作用而引起了相当大的科学关注。Nar 和 Que 对 mitoBK 通道门控的开放增强作用已经有报道。然而,相应的通道-配体相互作用的分子图景仍然有待揭示。在这项工作中,我们研究了 Nar 和 Que 对 mitoBK 通道构象动力学的影响。为此,采用膜片钳方法记录的单通道信号进行基于互相关的分析。以相空间图的形式获得的结果使我们能够直观地监测所考虑的类黄酮在重复通道构象序列的时间特征水平上施加的影响。结果表明,柚皮素和槲皮素激活 mitoBK 通道不会导致相空间图中簇的数量发生变化,这可以与无论是否施用类黄酮,可用通道宏观构象的数量保持不变相关联。互相关序列簇的定位和占据表明,类黄酮刺激 mitoBK 通道会影响通道构象的相对稳定性及其之间转换的动力学。对于大多数簇,与柚皮素相比,槲皮素给药时观察到更大的净效应。这表明与 Nar 相比,Que 与通道的相互作用更强。