Abstract

AbstractVisual 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.

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