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Ca2+ Release Channels Join the 'Resolution Revolution'.

ABSTRACT: Ryanodine receptors (RyRs) are calcium release channels expressed in the sarcoendoplasmic reticula of many cell types including cardiac and skeletal muscle cells. In recent years Ca2+ leak through RyRs has been implicated as a major contributor to the development of diseases including heart failure, muscle myopathies, Alzheimer's disease, and diabetes, making it an important therapeutic target. Recent mammalian RyR1 cryoelectron microscopy (cryo-EM) structures of multiple functional states have clarified longstanding questions including the architecture of the transmembrane (TM) pore and cytoplasmic domains, the location and architecture of the channel gate, ligand-binding sites, and the gating mechanism. As we advance toward complete models of RyRs this new information enables the determination of domain-domain interfaces and the location and structural effects of disease-causing RyR mutations.

SUBMITTER: Zalk R

PROVIDER: S-EPMC5875148 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Ca<sup>2+</sup> Release Channels Join the 'Resolution Revolution'.

Zalk Ran R Marks Andrew R AR

Trends in biochemical sciences 20170509 7

Ryanodine receptors (RyRs) are calcium release channels expressed in the sarcoendoplasmic reticula of many cell types including cardiac and skeletal muscle cells. In recent years Ca<sup>2+</sup> leak through RyRs has been implicated as a major contributor to the development of diseases including heart failure, muscle myopathies, Alzheimer's disease, and diabetes, making it an important therapeutic target. Recent mammalian RyR1 cryoelectron microscopy (cryo-EM) structures of multiple functional s ...[more]

PMID: 28499500

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