Exploration of the dynamic interplay between lipids and membrane proteins by hydrostatic pressure

Alexandre Pozza (1) , François Giraud (2) , Quentin Cece (1, 3) , Marina Casiraghi (1, 4) , Elodie Point (1) , Marjorie Damian (5) , Christel Le Bon (1) , Karine Moncoq (1) , Jean-Louis Banères (5) , Ewen Lescop (2) , Laurent Catoire (1)

1 LBPC-PM (UMR_7099) - Laboratoire de biologie physico-chimique des protéines membranaires
2 ICSN - Institut de Chimie des Substances Naturelles
3 CiTCoM - UMR 8038 - Cibles Thérapeutiques et conception de médicaments
4 Department of Molecular and Cellular Physiology [Stanford]
5 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

Cell membranes represent a complex and variable medium in time and space of lipids and proteins. Their physico-chemical properties are determined by lipid components which can in turn influence the biological function of membranes. Here, we used hydrostatic pressure to study the close dynamic relationships between lipids and membrane proteins. Experiments on the β –barrel OmpX and the α –helical BLT2 G Protein-Coupled Receptor in nanodiscs of different lipid compositions reveal conformational landscapes intimately linked to pressure and lipids. Pressure can modify the conformational landscape of the membrane protein per se, but also increases the gelation of lipids, both being monitored simultaneously at high atomic resolution by NMR. Our study also clearly shows that a membrane protein can modulate, at least locally, the fluidity of the bilayer. The strategy proposed herein opens new perspectives to scrutinize the dynamic interplay between membrane proteins and their surrounding lipids.

Mots clés: Solution-state NMR; NMR spectroscopy; Molecular conformation; Membrane biophysics; G protein-coupled receptors

Domaines: Biochimie, Biologie Moléculaire

Alexandre Pozza, François Giraud, Quentin Cece, Marina Casiraghi, Elodie Point, et al.. Exploration of the dynamic interplay between lipids and membrane proteins by hydrostatic pressure. Nature Communications, 2022, 13 (1), pp.1780. ⟨10.1038/s41467-022-29410-5⟩. ⟨hal-03665500⟩