The boundary lipid around DMPC-spanning influenza A M2 transmembrane domain channels: Its structure and potential for drug accommodation

Publication date: Available online 14 December 2019Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Athina Konstantinidi, Maria Chountoulesi, Nikolaos Naziris, Barbara Sartori, Heinz Amenitsch, Gregor Mali, Tomaž Čendak, Maria Plakantonaki, Iro Triantafyllakou, Theodore Tselios, Costas Demetzos, David D. Busath, Thomas Mavromoustakos, Antonios KolocourisAbstractWe have investigated the perturbation of influenza A M2TM in DMPC bilayers. We have shown that (a) DSC and SAXS detect changes in membrane organization caused by small changes (micromolar) in M2TM or aminoadamantane concentration and aminoadamantane structure, by comparison of amantadine and spiro[pyrrolidine-2,2′-adamantane] (AK13), (b) that WAXS and MD can suggest details of ligand topology. DSC and SAXS show that at a low M2TM micromolar concentration in DPMC bilayers, two lipid domains are observed, which likely correspond to M2TM boundary lipids and bulk-like lipids. At higher M2TM concentrations, one domain only is identified, which constitutes essentially all of the lipid molecules behaving as boundary lipids. According to SAXS, WAXS, and DSC in the absence of M2TM, both aminoadamantane drugs exert a similar perturbing effect on the bilayer at low concentrations. At the same concentrations of the drug when M2TM is present, amantadine and, to a lesser extent, AK13 cause, according to WAXS, a significant disordering of chain-stacking, which also leads to the formation of two lipid domains. ...
Source: Biochimica et Biophysica Acta (BBA) Biomembranes - Category: Biochemistry Source Type: research