Allosteric coupling between a lipid bilayer and a membrane protein

Biological membranes are complex environments whose functions are closely tied to the dynamic interactions between lipids and proteins. Here, we utilize high-pressure NMR of lipid nanodiscs paired with molecular dynamics simulations to elucidate at the atomic scale the allosteric dialog between the lipid bilayer and a model membrane protein, OmpX. We discover that OmpX delays the gelation process by liquefying the annular shell of lipids through hydrophobic and roughness matching processes at the protein surface. Furthermore, modification of the mechanical properties of the lipid bilayer directly impacts the energy landscape of amino acid side chains at the lipid/protein interface but also unexpectedly at the protein core. Our work highlights a thermodynamically coupled but kinetically uncoupled allosteric pathway linking lipid dynamics with the interior of membrane proteins, directly impacting our understanding of membrane function.