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PDBsum entry 4uwa
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Signaling protein
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PDB id
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4uwa
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References listed in PDB file
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Key reference
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Title
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Architecture and conformational switch mechanism of the ryanodine receptor.
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Authors
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R.G.Efremov,
A.Leitner,
R.Aebersold,
S.Raunser.
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Ref.
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Nature, 2015,
517,
39-43.
[DOI no: ]
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PubMed id
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Abstract
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Muscle contraction is initiated by the release of calcium (Ca(2+)) from the
sarcoplasmic reticulum into the cytoplasm of myocytes through ryanodine
receptors (RyRs). RyRs are homotetrameric channels with a molecular mass of more
than 2.2 megadaltons that are regulated by several factors, including ions,
small molecules and proteins. Numerous mutations in RyRs have been associated
with human diseases. The molecular mechanism underlying the complex regulation
of RyRs is poorly understood. Using electron cryomicroscopy, here we determine
the architecture of rabbit RyR1 at a resolution of 6.1 Å. We show that the
cytoplasmic moiety of RyR1 contains two large α-solenoid domains and several
smaller domains, with folds suggestive of participation in protein-protein
interactions. The transmembrane domain represents a chimaera of voltage-gated
sodium and pH-activated ion channels. We identify the calcium-binding EF-hand
domain and show that it functions as a conformational switch allosterically
gating the channel.
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