Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
Biophys J. 2010 Aug 4;99(3):L29-31. doi: 10.1016/j.bpj.2010.05.018.
Allosteric transitions of ion channels can be driven by multiple sources of free energies. One class of model for describing such transitions is the multistimulus Monod-Wyman-Changeux model, in which each stimulus interacts with a specific sensor on the protein and activation of the sensor is allosterically coupled to conformational changes of the protein. In general, when a protein is stressed by multiple stimuli, one stimulus can influence the response to another, which can result in both a shift of the midpoint of the dose-response curve and a change of the slope of the curve. Here I show that, for a Monod-Wyman-Changeux model with independent sensors, the different dose-response curves of open probability for one stimulus have the same slope at the same agonist concentration. In the other words, the slope of the dose-response curve for one stimulus is an intrinsic property of the sensors for that stimulus; it is independent of other stimuli or their sensor properties. As the dose-response curve for many receptors can be fit to a Boltzmann or Hill equation, this property provides a practical, usable test for applicability of such models.
离子通道的变构跃迁可以由多种自由能来源驱动。描述这种跃迁的一类模型是多刺激莫诺德-韦曼-钱卓模型，其中每个刺激与蛋白质上的特定传感器相互作用，传感器的激活与蛋白质的构象变化呈变构偶联。一般来说，当蛋白质受到多种刺激时，一种刺激可以影响对另一种刺激的反应，这可能导致剂量反应曲线的中点发生位移，以及曲线斜率的变化。在这里，我表明，对于具有独立传感器的莫诺德-韦曼-钱卓模型，一个刺激的开放概率的不同剂量反应曲线在相同的激动剂浓度下具有相同的斜率。换句话说，一个刺激的剂量反应曲线的斜率是该刺激传感器的固有特性；它独立于其他刺激或其传感器特性。由于许多受体的剂量反应曲线可以拟合为玻尔兹曼或希尔方程，因此该特性为这些模型的适用性提供了一种实用的、可用的测试。
