Structural Details of the Ryanodine Receptor Calcium Release Channel and Its Gating Mechanism

Katrien Willegems, Rouslan G Efremov

Research output: Book/ReportBook

3 Citations (Scopus)

Abstract

Ryanodine receptors (RyRs) are large intracellular calcium release channels that play a crucial role in coupling excitation to contraction in both cardiac and skeletal muscle cells. In addition, they are expressed in other cell types where their function is less well understood. Hundreds of mutations in the different isoforms of RyR have been associated with inherited myopathies and cardiac arrhythmia disorders. The structure of these important drug targets remained elusive for a long time, despite decades of intensive research. In the recent years, a technical revolution in the field of single particle cryogenic electron microscopy (SP cryo-EM) allowed solving high-resolution structures of the skeletal and cardiac RyR isoforms. Together with the structures of individual domains solved by X-ray crystallography, this resulted in an unprecedented understanding of the structure, gating and regulation of these largest known ion channels. In this chapter we describe the recently solved high-resolution structures of RyRs, discuss molecular details of the channel gating, regulation and the disease mutations. Additionally, we highlight important questions that require further progress in structural studies of RyRs.

Original languageEnglish
PublisherSpringer
Number of pages26
Volume981
ISBN (Electronic)978-3-319-55858-5
ISBN (Print)978-3-319-55857-8
DOIs
Publication statusPublished - 2017

Publication series

NameAdvances in Experimental Medicine and Biology
PublisherSpringer New York
ISSN (Print)0065-2598

Keywords

  • Animals
  • Calcium/chemistry
  • Calcium Signaling
  • Humans
  • Ion Channel Gating
  • Muscle, Skeletal/chemistry
  • Mutation
  • Myocardium/chemistry
  • Protein Domains
  • Protein Isoforms/chemistry
  • Ryanodine Receptor Calcium Release Channel/chemistry
  • Structure-Activity Relationship

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