Influence of Lipid Mimetics on Gating of Ryanodine Receptor
| Autor: | Rouslan G. Efremov, Katrien Willegems |
|---|---|
| Přispěvatelé: | Structural Biology Brussels, Department of Bio-engineering Sciences |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Models Molecular Detergents Lipid Bilayers Molecular Conformation chemistry.chemical_element Gating Calcium 03 medical and health sciences 0302 clinical medicine Structural Biology nanostructures Myocyte Animals Molecular Biology Ion channel Calcium signaling RYR1 Ryanodine receptor Chemistry Endoplasmic reticulum Cryoelectron Microscopy Ryanodine Receptor Calcium Release Channel Ryanodine Receptor Calcium Release Channel/chemistry musculoskeletal system 030104 developmental biology Detergents/metabolism Lipid Bilayers/metabolism Biophysics Rabbits tissues Ion Channel Gating 030217 neurology & neurosurgery |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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