Ranatunga Kishani M, Chen S R Wayne, Ruest Luc, Welch William, Williams Alan J
Cardiac Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
Mol Membr Biol. 2007 May-Jun;24(3):185-93. doi: 10.1080/09687860601076522.
Understanding the nature of the interaction of the plant alkaloid ryanodine with its receptor channel (RyR) is important to aid interpretation of physiological studies and provide structure-function information about RyR. We present here the first quantitative description of the relative single-channel kinetic effects of a single-point mutation in RyR2. We exploit the well-characterized ryanoid 8beta-amino-9alpha-hydroxyryanodine that displays reversible kinetics with RyR2. We explicitly show that the effect of the Q4863A mutation is to increase the apparent dissociation constant by increasing the apparent dissociation rate of the ryanoid. The voltage-dependence of the interaction displays no change. We infer that Q4863 is not involved with the voltage-drop but is able to influence ryanoid-bound structural changes. We discuss structural mechanisms by which this mutation could affect ryanoid interaction.
了解植物生物碱雷诺丁与其受体通道（RyR）的相互作用本质，对于辅助解释生理学研究以及提供有关RyR的结构-功能信息非常重要。我们在此展示了对RyR2中单点突变的相对单通道动力学效应的首次定量描述。我们利用了特征明确的类雷诺丁8β-氨基-9α-羟基雷诺丁，它与RyR2呈现可逆动力学。我们明确表明，Q4863A突变的作用是通过增加类雷诺丁的表观解离速率来提高表观解离常数。相互作用的电压依赖性没有变化。我们推断，Q4863不参与电压降，但能够影响与类雷诺丁结合的结构变化。我们讨论了这种突变可能影响类雷诺丁相互作用的结构机制。
