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TitleInfluence of Lipid Mimetics on Gating of Ryanodine Receptor.
Journal, issue, pagesStructure, Vol. 26, Issue 10, Page 1303-11313.e4, Year 2018
Publish dateOct 2, 2018
AuthorsKatrien Willegems / Rouslan G Efremov /
PubMed AbstractUnderstanding 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) ...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.
External linksStructure / PubMed:30078641
MethodsEM (single particle)
Resolution7.3 - 8.2 Å
Structure data

4258

6fg3

EMDB-4258, PDB-6fg3:
Structure of Ryanodine receptor 1 in nanodiscs in the presence of calcium, ATP and ryanodine
Method: EM (single particle) / Resolution: 7.3 Å

4295

6foo

EMDB-4295, PDB-6foo:
Structure of Ryanodine Receptor 1 in nanodiscs in the presence of calcium and ATP
Method: EM (single particle) / Resolution: 8.2 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-CA:
Unknown entry

Source
  • oryctolagus cuniculus (rabbit)
KeywordsMEMBRANE PROTEIN / calcium release channel / nanodiscs

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