Structure of a mammalian ryanodine receptor

Ryanodine receptors (RyRs) mediate rapid release of calcium (Ca2+) from intracellular stores into the cytosol, which is essential for numerous cellular functions including excitation-contraction coupling in muscle. Lack of sufficient structural detail has impeded understanding of RyR gating and regu...

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Main Authors:	Zalk, Ran, Clarke, Oliver B., des Georges, Amédée, Grassucci, Robert A., Reiken, Steven, Mancia, Filippo, Hendrickson, Wayne A., Frank, Joachim, Marks, Andrew R.
Format:	Online
Language:	English
Published:	2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300236/

id	pubmed-4300236
recordtype	oai_dc
spelling	pubmed-43002362015-07-01 Structure of a mammalian ryanodine receptor Zalk, Ran Clarke, Oliver B. des Georges, Amédée Grassucci, Robert A. Reiken, Steven Mancia, Filippo Hendrickson, Wayne A. Frank, Joachim Marks, Andrew R. Article Ryanodine receptors (RyRs) mediate rapid release of calcium (Ca2+) from intracellular stores into the cytosol, which is essential for numerous cellular functions including excitation-contraction coupling in muscle. Lack of sufficient structural detail has impeded understanding of RyR gating and regulation. Here, we report the closed-state structure of the 2.3 MDa complex of the rabbit skeletal muscle type 1 RyR (RyR1), solved by single-particle cryo-electron microscopy at an overall resolution of 4.8 Å. We fitted a polyalanine-level model to all 3939 ordered residues in each protomer, defining the transmembrane pore in unprecedented detail and placing all cytosolic domains as tertiary folds. The cytosolic assembly is built on an extended α-solenoid scaffold connecting key regulatory domains to the pore. The RyR1 pore architecture places it in the six-transmembrane (6TM) ion channel superfamily. A unique domain inserted between the second and third transmembrane helices interacts intimately with paired EF-hands originating from the α-solenoid scaffold, suggesting a mechanism for channel gating by Ca2+. 2014-12-01 2015-01-01 /pmc/articles/PMC4300236/ /pubmed/25470061 http://dx.doi.org/10.1038/nature13950 Text en Reprints and permissions information is available at www.nature.com/reprints
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zalk, Ran Clarke, Oliver B. des Georges, Amédée Grassucci, Robert A. Reiken, Steven Mancia, Filippo Hendrickson, Wayne A. Frank, Joachim Marks, Andrew R.
spellingShingle	Zalk, Ran Clarke, Oliver B. des Georges, Amédée Grassucci, Robert A. Reiken, Steven Mancia, Filippo Hendrickson, Wayne A. Frank, Joachim Marks, Andrew R. Structure of a mammalian ryanodine receptor
author_facet	Zalk, Ran Clarke, Oliver B. des Georges, Amédée Grassucci, Robert A. Reiken, Steven Mancia, Filippo Hendrickson, Wayne A. Frank, Joachim Marks, Andrew R.
author_sort	Zalk, Ran
title	Structure of a mammalian ryanodine receptor
title_short	Structure of a mammalian ryanodine receptor
title_full	Structure of a mammalian ryanodine receptor
title_fullStr	Structure of a mammalian ryanodine receptor
title_full_unstemmed	Structure of a mammalian ryanodine receptor
title_sort	structure of a mammalian ryanodine receptor
description	Ryanodine receptors (RyRs) mediate rapid release of calcium (Ca2+) from intracellular stores into the cytosol, which is essential for numerous cellular functions including excitation-contraction coupling in muscle. Lack of sufficient structural detail has impeded understanding of RyR gating and regulation. Here, we report the closed-state structure of the 2.3 MDa complex of the rabbit skeletal muscle type 1 RyR (RyR1), solved by single-particle cryo-electron microscopy at an overall resolution of 4.8 Å. We fitted a polyalanine-level model to all 3939 ordered residues in each protomer, defining the transmembrane pore in unprecedented detail and placing all cytosolic domains as tertiary folds. The cytosolic assembly is built on an extended α-solenoid scaffold connecting key regulatory domains to the pore. The RyR1 pore architecture places it in the six-transmembrane (6TM) ion channel superfamily. A unique domain inserted between the second and third transmembrane helices interacts intimately with paired EF-hands originating from the α-solenoid scaffold, suggesting a mechanism for channel gating by Ca2+.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300236/
_version_	1613178594321760256

Structure of a mammalian ryanodine receptor

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