Activation of the G-Protein-Coupled Receptor Rhodopsin by Water

Udeep Chawla, Suchithranga M. D. C. Perera, Steven D. E. Fried, Anna R. Eitel, Blake Mertz, Nipuna Weerasinghe, Michael C. Pitman, Andrey Struts, M.F. Brown

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.
Translated title of the contributionАктивация рецептора сопряженного с Г-белком родопсина водой
Original languageEnglish
Pages (from-to)2288-2295
JournalAngewandte Chemie - International Edition
Volume60
Issue number5
Early online date28 Jun 2020
DOIs
StatePublished - 1 Feb 2021

Scopus subject areas

  • Chemistry(all)
  • Catalysis

Keywords

  • GPCRs
  • membrane lipids
  • membrane proteins
  • osmotic stress
  • rhodopsin
  • CRYSTAL-STRUCTURE
  • METARHODOPSIN
  • RETINAL LIGAND
  • RELAXATION
  • INTERNAL HYDRATION
  • PRESSURE DENATURATION
  • VOLUMETRIC PROPERTIES
  • OPIOID RECEPTOR
  • DYNAMICS
  • REVEALS CONFORMATIONAL EQUILIBRIA

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