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• W3100190058 endingPage "452" @default.
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• W3100190058 abstract "G-protein-coupled receptors (GPCRs) comprise the largest and most pharmacologically targeted membrane protein family. Here, we used the visual receptor rhodopsin as an archetype for understanding membrane lipid influences on conformational changes involved in GPCR activation. Visual rhodopsin was recombined with lipids varying in their degree of acyl chain unsaturation and polar headgroup size using 1-palmitoyl-2-oleoyl-sn-glycero- and 1,2-dioleoyl-sn-glycerophospholipids with phosphocholine (PC) or phosphoethanolamine (PE) substituents. The receptor activation profile after light excitation was measured using time-resolved ultraviolet-visible spectroscopy. We discovered that more saturated POPC lipids back shifted the equilibrium to the inactive state, whereas the small-headgroup, highly unsaturated DOPE lipids favored the active state. Increasing unsaturation and decreasing headgroup size have similar effects that combine to yield control of rhodopsin activation, and necessitate factors beyond proteolipid solvation energy and bilayer surface electrostatics. Hence, we consider a balance of curvature free energy with hydrophobic matching and demonstrate how our data support a flexible surface model (FSM) for the coupling between proteins and lipids. The FSM is based on the Helfrich formulation of membrane bending energy as we previously first applied to lipid-protein interactions. Membrane elasticity and curvature strain are induced by lateral pressure imbalances between the constituent lipids and drive key physiological processes at the membrane level. Spontaneous negative monolayer curvature toward water is mediated by unsaturated, small-headgroup lipids and couples directly to GPCR activation upon light absorption by rhodopsin. For the first time to our knowledge, we demonstrate this modulation in both the equilibrium and pre-equilibrium evolving states using a time-resolved approach." @default.
• W3100190058 created "2020-11-23" @default.
• W3100190058 creator A5005781724 @default.
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• W3100190058 creator A5090097436 @default.
• W3100190058 date "2021-02-01" @default.
• W3100190058 modified "2023-10-14" @default.
• W3100190058 title "Membrane Curvature Revisited—the Archetype of Rhodopsin Studied by Time-Resolved Electronic Spectroscopy" @default.
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• W3100190058 doi "https://doi.org/10.1016/j.bpj.2020.11.007" @default.
• W3100190058 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7896002" @default.
• W3100190058 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33217383" @default.
• W3100190058 hasPublicationYear "2021" @default.

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