PDBsum entry 4uwa

Signaling protein

PDB id: 4uwa

Contents

Protein chains

3324 a.a.

PDB id:

4uwa

Name:

Signaling protein

Title:

Structure of the ryanodine receptor at resolution of 6.1 a in closed state

Structure:

Ryanodine receptor 1. Chain: a, b, c, d. Synonym: ryr-1, ryr1, skeletal muscle calcium release channel, skeletal muscle ryanodine receptor, skeletal muscle-type ryanodine receptor, type 1 ryanodine receptor

Source:

Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Organ: sarcoplasmic reticulum. Tissue: muscle. Cell: myocyte

Authors:

R.G.Efremov,A.Leitner,R.Aebersold,S.Raunser

Key ref:

R.G.Efremov et al. (2015). Architecture and conformational switch mechanism of the ryanodine receptor. Nature, 517, 39-43. PubMed id: 25470059 DOI: 10.1038/nature13916

Date:

11-Aug-14 Release date: 10-Dec-14

Protein chains

P11716  (RYR1_RABIT) -  Ryanodine receptor 1 from Oryctolagus cuniculus

Seq: 5037 a.a.

Struc: 3324 a.a.*

* PDB and UniProt seqs differ at 2193 residue positions (black crosses)

DOI no: 10.1038/nature13916

Nature 517:39-43 (2015)

PubMed id: 25470059

Architecture and conformational switch mechanism of the ryanodine receptor.

R.G.Efremov, A.Leitner, R.Aebersold, S.Raunser.

ABSTRACT

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.