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Membrane Dynamics and Calcium Signaling pp 179–204Cite as

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

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 981))

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.

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Acknowledgements

This work was funded by grants from VIB, FWO grant number G.0266.15N and IWT fellowship number 131261 to K.W.

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Authors and Affiliations

  1. Center for Structural Biology, Vlaams Instituut voor Biotechnologie, Brussels, Belgium

    Katrien Willegems & Rouslan G. Efremov

  2. Structural Biology Brussels, Department of Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium

    Katrien Willegems & Rouslan G. Efremov

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  1. Katrien Willegems
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  2. Rouslan G. Efremov
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Correspondence to Rouslan G. Efremov .

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  1. MPI for Biophysical Chemistry, Göttingen, Germany

    Joachim Krebs

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Willegems, K., Efremov, R.G. (2017). Structural Details of the Ryanodine Receptor Calcium Release Channel and Its Gating Mechanism. In: Krebs, J. (eds) Membrane Dynamics and Calcium Signaling. Advances in Experimental Medicine and Biology, vol 981. Springer, Cham. https://doi.org/10.1007/978-3-319-55858-5_8

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