Vlaams Instituut voor Biotechnologie
Concentration of calcium ions in the cytoplasm of cells regulates many physiological processes, including transcription, cell cycle, apoptosis, and muscular contraction. Muscles are contracted at high calcium concentrations and relaxed at low calcium concentrations in the cytoplasm, and contraction is initiated by the release of Ca2+ from the sarcoplasmic reticulum into the cytoplasm of myocytes through ryanodine receptors (RyR). RyRs are the 2.2 MDa homotetrameric ion channels that are primarily gated by changes in concentration of calcium ions in the cytoplasm, and are regulated by multiple factors, including ions, small organic molecules, and interactions with other proteins. Hundreds of mutations in RyRs have been associated with human diseases, but the molecular mechanism underlying the complex regulation of RyR is still poorly understood. I will present the architecture of rabbit RyR1 determined at resolution of 6.1 Å by single particle cryo-EM, and show how changes in calcium concentration induce conformational changes in RyR resulting in the channel gating.