期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 5, 页码 2288-2295出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202003342
关键词
GPCRs; membrane lipids; membrane proteins; osmotic stress; rhodopsin
资金
- NSF [CHE 1904125, MCB 1817862]
- NIH [EY012049, EY026041, EY014614]
- Technology Research Initiative Fund (TRIF) predoctoral fellowship from the Arizona Board of Regents
- Goldwater research scholarship
- University of Arizona
- Russian Foundation for Basic Research [16-04-00494A]
Visual rhodopsin absorbs light and takes in approximately 80 water molecules to form a solvent-swollen active state, which is essential for activating the photoreceptor and is supported by molecular dynamics simulations. Force-based measurements show that the expansion of rhodopsin occurs through changes in cavity volumes and increased hydration in the active Meta II state. Furthermore, the binding and release of the C-terminal helix of transducin is coupled to hydration changes, potentially influencing visual signal amplification through a dynamic allosteric mechanism involving lipid and water interactions in the catalytic G-protein cycle.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据