August 11, 2025 -- August 11, 2025
Speaker : Dr. Georg Pabst, Univ. of Graz, Institute of Molecular Biosciences, Graz, Austria.
Date & Time: 11-Aug. 2025-Monday, at 4 PM.
Venue : Seminar Hall, Chemical Engg.
Allosteric Modulation of Integral Protein Activity by Differential Lateral Stress in Asymmetric Membranes.
Lipid asymmetry is a defining feature of plasma membranes, yet its impact on integral membrane protein function remains incompletely understood [1]. One proposed mechanism involves asymmetric lateral stress between membrane leaflets influencing protein conformational equilibria. To explore this, we employed bottom-up strategies to construct synthetic asymmetric lipid bilayers and reconstituted the outer membrane phospholipase A (OmpLA) into these model systems. Using bilayers composed of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol, we quantified OmpLA activity under defined compositional asymmetries.
We found that lipid asymmetry significantly modulates OmpLA function: enzymatic activity was reduced in charge-neutral asymmetric membranes but enhanced in charged asymmetric environments. Remarkably, monovalent ions—traditionally not considered protein cofactors—further influenced the enzyme’s activity [2, 3]. These observations are consistent with allosteric modulation arising from differences in spontaneous monolayer curvatures between membrane leaflets and its regulation by ionic conditions.
Our findings point to a general mechanism by which lipid asymmetry and ion–lipid interactions dynamically regulate membrane protein function, with broad implications for understanding membrane physiology and signalling.
