title: Hydrogen bonding of cholesterol in the lipidic cubic phase.
abstract: The addition of cholesterol to the monoolein-based lipidic cubic phase (LCP) has been instrumental in obtaining high-resolution crystal structures of several G protein-coupled receptors. Here, we report the use of high-resolution magic angle spinning NMR spectroscopy to record and assign the isotropic (13)C chemical shifts of cholesterol in lipidic lamellar and cubic phases at different hydration levels with monoolein and chain-deuterated DMPC as host lipids. The hydrogen-bonding patterns of cholesterol in these phases were determined from the NMR data by quantum chemical calculations. The results are consistent with the normal orientation of cholesterol in lipid bilayers and with the cholesterol hydroxyl group located at the hydrophobic/hydrophilic interface. The (13)C chemical shifts of cholesterol are mostly affected by the host lipid identity with little or no dependency on the hydration (20% vs 40%) or the phase identity (lamellar vs LCP). In chain-deuterated DMPC bilayers, the hydroxyl group of cholesterol forms most of its hydrogen bonds with water, while in monoolein bilayers it predominately interacts with monoolein. Such differences in the hydrogen-bonding network of cholesterol may have implications for the design of experiments in monoolein-based LCP.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, UMR 5089, CNRS - Université de Toulouse, UPS BP 64182, 205 route de Narbonne, 31077 Toulouse, Cedex04, France.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Gater
authors.forename: Valérie
authors.initials: V
authors.lastname: Réat
authors.forename: Georges
authors.initials: G
authors.lastname: Czaplicki
authors.forename: Olivier
authors.initials: O
authors.lastname: Saurel
authors.forename: Alain
authors.initials: A
authors.lastname: Milon
authors.forename: Franck
authors.initials: F
authors.lastname: Jolibois
authors.forename: Vadim
authors.initials: V
authors.lastname: Cherezov
mesh_terms: D002784:Cholesterol / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods
chemical_list: D002784:Cholesterol