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Functional characterization of the cardiac Ryanodine receptor pore-forming region

Euden, Joanne, Mason, Sammy and Williams, Alan John 2013. Functional characterization of the cardiac Ryanodine receptor pore-forming region. PLoS ONE 8 (6) , e66542. 10.1371/journal.pone.0066542

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Abstract

Ryanodine receptors are homotetrameric intracellular calcium release channels. The efficiency of these channels is underpinned by exceptional rates of cation translocation through the open channel and this is achieved at the expense of the high degree of selectivity characteristic of many other types of channel. Crystallization of prokaryotic potassium channels has provided insights into the structures and mechanisms responsible for ion selection and movement in these channels, however no equivalent structural detail is currently available for ryanodine receptors. Nevertheless both molecular modeling and cryo-electron microscopy have identified the probable pore-forming region (PFR) of the ryanodine receptor (RyR) and suggest that this region contains structural elements equivalent to those of the PFRs of potassium-selective channels. The aim of the current study was to establish if the isolated putative cardiac RyR (RyR2) PFR could form a functional ion channel. We have expressed and purified the RyR2 PFR and shown that function is retained following reconstitution into planar phospholipid bilayers. Our data provide the first direct experimental evidence to support the proposal that the conduction pathway of RyR2 is formed by structural elements equivalent to those of the potassium channel PFR.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine
Publisher: Public Library of Science
ISSN: 1932-6203
Funders: British Heart Foundation
Date of First Compliant Deposit: 30 March 2016
Last Modified: 12 Jun 2019 02:29
URI: http://orca.cf.ac.uk/id/eprint/60468

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