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We review osmotic stress studies of the G-protein-coupled receptor rhodopsin. Despite the established presence of small amounts of structural water in these receptors, the influence of bulk water on their function remains unknown. Investigations of osmotic stress effects on the GPCR archetype rhodopsin have provided unique data about the role of water in receptor activation. It was discovered that osmolytes shift the rhodopsin equilibrium after photoactivation, either to the active or inactive conformations depending on their molar mass. Experimentally at least 80 water molecules have been found to enter rhodopsin in the transition to the active state. We propose that this influx of water is a necessary condition for receptor activation. If the water movement is blocked, e.g., by large osmolytes or by dehydration, then the receptor does not undergo its functional transition. The results suggest a new model whereby rhodopsin becomes swollen and partially unfolded in the activation mechanism. Water thus acts as a powerful allosteric modulator of functioning for rhodopsin-like receptors. Keywords: G-protein-coupled receptors, membranes, optical spectroscopy, rhodopsin, signal transduction.
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Osmotic stress studies of G-protein-coupled receptor rhodopsin activation
We summarize and critically review osmotic stress studies of the G-protein-coupled receptor rhodopsin. Although small amounts of structural water are present in these receptors, the effect of bulk water on their function remains uncertain. Studies of the influences of osmotic stress on the GPCR archetype rhodopsin have given insights into the functional role of water in receptor activation. Experimental work has discovered that osmolytes shift the metarhodopsin equilibrium after photoactivation, either to the active or inactive conformations according to their molar mass. At least 80 water molecules are found to enter rhodopsin in the transition to the photoreceptor active state. We infer that this movement of water is both necessary and sufficient for receptor activation. If the water influx is prevented, e.g., by large polymer osmolytes or by dehydration, then the receptor functional transition is back shifted. These findings imply a new paradigm in which rhodopsin becomes solvent swollen in the activation mechanism. Water thus acts as an allosteric modulator of function for rhodopsin-like receptors in lipid membranes.
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- PAR ID:
- 10526249
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- Biophysical Chemistry
- Volume:
- 304
- ISSN:
- 0301-4622
- Page Range / eLocation ID:
- 107112
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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