Architecture and conformational switchmechanism of the ryanodine receptor

Ruslan Efremov, Alexander Leitner, Ruedi Aebersold, Stefan Raunser

Research output: Contribution to journalArticle

204 Citations (Scopus)


Muscle contraction is initiated by the release of calcium (Ca21) from the sarcoplasmic reticulum into the cytoplasm of myocytes through ryanodine receptors (RyRs). RyRs are homotetrameric channels with a molecular mass of more than 2.2 megadaltons that are regulated by several factors, including ions, small molecules and proteins. Numerous mutations in RyRs have been associated with human diseases. The molecular mechanism underlying the complex regulation of RyRs is poorly understood. Using electron cryomicroscopy, here we determine the architecture of rabbit RyR1 at a resolution of 6.1 A . We show that the cytoplasmic moiety of RyR1 contains two large a-solenoid domains and several smaller domains, with folds suggestive of participation in protein-protein interactions. The transmembrane domain represents a chimaera of voltage-gated sodium and pH-activated ion channels. We identify the calcium-binding EF-hand domain and show that it functions as a conformational switch allosterically gating the channel.
Original languageEnglish
Pages (from-to)39-43
Issue number7532
Publication statusPublished - 1 Jan 2015


  • ion channel
  • membrane protein
  • muscle
  • cryo-EM
  • single particle


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