Hydrogen Bonding of Cholesterol in the Lipidic Cubic Phase

Deborah Gater , Valérie Réat (1) , Georges Czaplicki (1) , Olivier Saurel (1) , Franck Jolibois (2) , Vadim Cherezov (3) , Alain Milon (1)

1 IPBS - Institut de pharmacologie et de biologie structurale
2 LPCNO - Laboratoire de physique et chimie des nano-objets
3 USC - University of Southern California

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 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.

Mots clés: ab initio calculations; monoolein; NMR spectroscopy; sterol-membrane interactions; HRMAS

Domaines: Biologie structurale [q-bio.BM]

Deborah Gater, Valérie Réat, Georges Czaplicki, Olivier Saurel, Franck Jolibois, et al.. Hydrogen Bonding of Cholesterol in the Lipidic Cubic Phase. Langmuir, 2013, 29 (25), pp.8031-8038. ⟨10.1021/la401351w⟩. ⟨hal-02322220⟩