Activation of the G‐Protein‐Coupled Receptor Rhodopsin by Water
| Autor: | Blake Mertz, Steven D. E. Fried, Michael F. Brown, Michael C. Pitman, Udeep Chawla, Nipuna Weerasinghe, Andrey V. Struts, Suchithranga M. D. C. Perera, Anna R. Eitel |
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| Rok vydání: | 2020 |
| Předmět: |
Rhodopsin
genetic structures Osmotic shock biology 010405 organic chemistry Chemistry Membrane lipids Allosteric regulation Hydrostatic pressure Water General Medicine General Chemistry 010402 general chemistry 01 natural sciences Catalysis Receptors G-Protein-Coupled 0104 chemical sciences Membrane protein Biophysics biology.protein Humans sense organs Transducin G protein-coupled receptor |
| Zdroj: | Angewandte Chemie International Edition. 60:2288-2295 |
| ISSN: | 1521-3773 1433-7851 |
| DOI: | 10.1002/anie.202003342 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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