The local lipid annulus, or "fingerprint", of four SLC6 transporters (dDAT, hDAT, hSERT, and GlyT2) embedded in a complex neuronal membrane were compared and characterised using molecular dynamics. Our analysis included the development of new tools to improve membrane leaflet detection and the analysis of leaflet-dependent properties. Overall, the lipid fingerprints of the four transporters are comprised of similar lipids when grouped by headgroup or tail saturation. The enrichment and depletion of specific lipids, including sites of cholesterol contacts, varies between transporters. The subtle differences in lipid fingerprints results in varying membrane biophysical properties near the transporter. Our results highlight that the lipid-fingerprint of SLC6 transporters in complex membranes is highly dependent on membrane composition. Our results further characterize how the presence and identity of membrane proteins affects the complex interplay of lipid-protein interactions, influencing the local lipid environment and membrane biophysical properties.
Keywords: SLC6 transport proteins; lLipid-protein interactions; mMembrane analysis; mMembrane transporters; mMolecular dynamics; nNeuronal membrane.
© 2021 The Authors. Published by Elsevier B.V.