Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA.
Laboratory of Biomolecular NMR, St. Petersburg State University, St. Petersburg, 199034, Russia.
Angew Chem Int Ed Engl. 2021 Feb 1;60(5):2288-2295. doi: 10.1002/anie.202003342. Epub 2020 Nov 27.
Visual rhodopsin is an important archetype for G-protein-coupled receptors, which are membrane proteins implicated in cellular signal transduction. Herein, we show experimentally that approximately 80 water molecules flood rhodopsin upon light absorption to form a solvent-swollen active state. An influx of mobile water is necessary for activating the photoreceptor, and this finding is supported by molecular dynamics (MD) simulations. Combined force-based measurements involving osmotic and hydrostatic pressure indicate the expansion occurs by changes in cavity volumes, together with greater hydration in the active metarhodopsin-II state. Moreover, we discovered that binding and release of the C-terminal helix of transducin is coupled to hydration changes as may occur in visual signal amplification. Hydration-dehydration explains signaling by a dynamic allosteric mechanism, in which the soft membrane matter (lipids and water) has a pivotal role in the catalytic G-protein cycle.
视紫红质是 G 蛋白偶联受体的重要原型，G 蛋白偶联受体是一种膜蛋白，参与细胞信号转导。在此，我们通过实验表明，在光吸收过程中，大约 80 个水分子涌入视紫红质，形成一个溶剂膨胀的活性状态。流动水的流入对于激活光感受器是必要的，这一发现得到了分子动力学（MD）模拟的支持。涉及渗透压和静水压的联合力测量表明，这种扩张是通过腔体积的变化以及活性视黄醛-II 状态下更大的水合作用来实现的。此外，我们发现，转导蛋白 C 端螺旋的结合和释放与水合变化有关，这种变化可能发生在视觉信号放大过程中。水合-去水合解释了信号转导的动态变构机制，其中软膜物质（脂质和水）在催化 G 蛋白循环中起着关键作用。
