Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Activation of the G-Protein-Coupled Receptor Rhodopsin by Water. / Chawla, Udeep; Perera, Suchithranga M. D. C.; Fried, Steven D. E.; Eitel, Anna R.; Mertz, Blake; Weerasinghe, Nipuna; Pitman, Michael C.; Struts, Andrey; Brown, M.F.
в: Angewandte Chemie - International Edition, Том 60, № 5, 01.02.2021, стр. 2288-2295.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Activation of the G-Protein-Coupled Receptor Rhodopsin by Water
AU - Chawla, Udeep
AU - Perera, Suchithranga M. D. C.
AU - Fried, Steven D. E.
AU - Eitel, Anna R.
AU - Mertz, Blake
AU - Weerasinghe, Nipuna
AU - Pitman, Michael C.
AU - Struts, Andrey
AU - Brown, M.F.
N1 - Publisher Copyright: © 2020 Wiley-VCH GmbH
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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.
AB - 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.
KW - GPCRs
KW - membrane lipids
KW - membrane proteins
KW - osmotic stress
KW - rhodopsin
KW - CRYSTAL-STRUCTURE
KW - METARHODOPSIN
KW - RETINAL LIGAND
KW - RELAXATION
KW - INTERNAL HYDRATION
KW - PRESSURE DENATURATION
KW - VOLUMETRIC PROPERTIES
KW - OPIOID RECEPTOR
KW - DYNAMICS
KW - REVEALS CONFORMATIONAL EQUILIBRIA
UR - http://www.scopus.com/inward/record.url?scp=85096641773&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/e87b6e11-c270-3f21-8384-0b81f18563f1/
U2 - 10.1002/anie.202003342
DO - 10.1002/anie.202003342
M3 - Article
VL - 60
SP - 2288
EP - 2295
JO - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
JF - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
SN - 1433-7851
IS - 5
ER -
ID: 60590991