Editorial: Novel insights into the modulation of protein function by lipids and membrane organization

Abstract

Editorial on the Research Topic Novel insights into the modulation of protein function by lipids and membrane organization Although the plasma membrane was originally thought to solely represent a passive diffusion barrier separating the intracellular and extracellular spaces, a growing body of evidence supports the active contribution of lipids and membrane organization to regulating the structure and function of transmembrane proteins. Furthermore, the tendency of biological membranes to segregate laterally into dynamic nano- and microdomains such as cholesterol-enriched lipid rafts and ceramide platforms, and their changes in response to altered lipid composition, add a further level of complexity to the active modulatory role of lipids in the functional regulation of proteins. After summarizing related literature cryo-EM data, the authors introduced a simplified computational model of the endoplasmic reticulum-localized sphingolipid flux, and analyzed the energetic contribution of single residues to ceramide binding by calculating the docking score and the predicted binding free energy for mutant SPT-ORMDL complexes, which, while not being validated experimentally in the study, are in agreement with recently published experimental data. Mechanosensitive ion channels, which play a substantial role in endothelial mechanotransduction and thus blood pressure regulation, are activated by mechanical forces, such as shear stress, a frictional force generated by the blood flow and membrane tension generated by stretch (Beverley et al., 2025) and their endothelial stiffening-induced functional alterations may contribute to cardiovascular disease and aging (Aguilar et al., 2022).