Influence of Lipid Mimetics on Gating of Ryanodine Receptor.

TitleInfluence of Lipid Mimetics on Gating of Ryanodine Receptor.
Publication TypeJournal Article
Year of Publication2018
AuthorsWillegems, K., and R. G. Efremov
Date Published2018 10 02
KeywordsAnimals, Cryoelectron Microscopy, Detergents, Ion Channel Gating, Lipid Bilayers, Male, Models, Molecular, Molecular Conformation, Nanostructures, Rabbits, Ryanodine Receptor Calcium Release Channel

Understanding gating principles of ion channels at high resolution is of great importance. Here we investigate the conformational transition from closed to open state in ryanodine receptor 1 (RyR1) reconstituted into lipid nanodiscs. RyR1 is a homotetrameric giant ion channel that couples excitation of muscle cells to fast calcium release from the sarcoplasmic reticulum. Using single-particle cryo-EM we show that RyR1 reconstituted into lipid nanodiscs is stabilized in the open conformation when bound to the plant toxin ryanodine, but not in the presence of its physiological activators, calcium and ATP. Further, using ryanodine binding assays we show that membrane mimetics influence RyR1 transition between closed and open-channel conformations. We find that all detergents, including fluorinated detergents added to nanodiscs, stabilize closed state of RyR1. Our biochemical results correlate with available structural data and suggest optimal conditions for structural studies of RyR1 gating.

Alternate JournalStructure
PubMed ID30078641
Research group: