[English] 日本語
Yorodumi
- EMDB-49542: Raw consensus map of mouse RyR1 (Ca2+/CFF/ATP dataset; closed pore) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-49542
TitleRaw consensus map of mouse RyR1 (Ca2+/CFF/ATP dataset; closed pore)
Map dataRaw consensus map of mouse RyR1 (Ca/CFF/ATP dataset; closed pore)
Sample
  • Complex: Complex of RyR1 with Calstabin-1 (Ca2+/CFF/ATP condition)
KeywordsCalcium / Ion Channel / Membrane Protein
Biological speciesMus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.4 Å
AuthorsWeninger G / Marks AR
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)R01 HL145473 United States
CitationJournal: J Clin Invest / Year: 2025
Title: Structural basis for simvastatin-induced skeletal muscle weakness associated with type 1 ryanodine receptor T4709M mutation.
Authors: Gunnar Weninger / Haikel Dridi / Steven Reiken / Qi Yuan / Nan Zhao / Linda Groom / Jennifer Leigh / Yang Liu / Carl Tchagou / Jiayi Kang / Alexander Chang / Estefania Luna-Figueroa / Marco ...Authors: Gunnar Weninger / Haikel Dridi / Steven Reiken / Qi Yuan / Nan Zhao / Linda Groom / Jennifer Leigh / Yang Liu / Carl Tchagou / Jiayi Kang / Alexander Chang / Estefania Luna-Figueroa / Marco C Miotto / Anetta Wronska / Robert T Dirksen / Andrew R Marks /
Abstract: Statins lower cholesterol, reducing the risk of heart disease, and are among the most frequently prescribed drugs. Approximately 10% of individuals develop statin-associated muscle symptoms (SAMS; ...Statins lower cholesterol, reducing the risk of heart disease, and are among the most frequently prescribed drugs. Approximately 10% of individuals develop statin-associated muscle symptoms (SAMS; myalgias, rhabdomyolysis, and muscle weakness), often rendering them statin intolerant. The mechanism underlying SAMS remains poorly understood. Patients with mutations in the skeletal muscle ryanodine receptor 1 (RyR1)/calcium release channel can be particularly intolerant of statins. High-resolution structures revealed simvastatin binding sites in the pore region of RyR1. Simvastatin stabilized the open conformation of the pore and activated the RyR1 channel. In a mouse expressing a mutant RyR1-T4709M found in a patient with profound statin intolerance, simvastatin caused muscle weakness associated with leaky RyR1 channels. Cotreatment with a Rycal drug that stabilizes the channel closed state prevented simvastatin-induced muscle weakness. Thus, statin binding to RyR1 can cause SAMS, and patients with RyR1 mutations may represent a high-risk group for statin intolerance.
History
DepositionMar 4, 2025-
Header (metadata) releaseJan 14, 2026-
Map releaseJan 14, 2026-
UpdateJan 14, 2026-
Current statusJan 14, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_49542.png

Downloads & links

-
Map

FileDownload / File: emd_49542.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationRaw consensus map of mouse RyR1 (Ca/CFF/ATP dataset; closed pore)
Voxel sizeX=Y=Z: 0.83 Å
Density
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.14558768 - 0.43395177
Average (Standard dev.)0.0016451613 (±0.017226404)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 424.96 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_49542_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_49542_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Complex of RyR1 with Calstabin-1 (Ca2+/CFF/ATP condition)

EntireName: Complex of RyR1 with Calstabin-1 (Ca2+/CFF/ATP condition)
Components
  • Complex: Complex of RyR1 with Calstabin-1 (Ca2+/CFF/ATP condition)

-
Supramolecule #1: Complex of RyR1 with Calstabin-1 (Ca2+/CFF/ATP condition)

SupramoleculeName: Complex of RyR1 with Calstabin-1 (Ca2+/CFF/ATP condition)
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 / Details: 0.03 mM free Ca2+; 5 mM Caffeine; 10 mM ATP
Source (natural)Organism: Mus musculus (house mouse)

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration8.5 mg/mL
BufferpH: 7.4
Component:
ConcentrationNameFormula
10.0 mmol/LHEPES
400.0 mmol/Lsodium chlorideNaCl
1.0 mmol/LEGTA
0.25 %CHAPS
0.01 %DOPC
0.5 mmol/LTCEP
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 4695 / Average electron dose: 58.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.2 µm / Nominal defocus min: 0.5 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionSoftware - Name: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL / In silico model: CryoSPARC ab initio
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 224439
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC / Details: CryoSPARC branch-and-bound
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC / Details: CryoSPARC branch-and-bound

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more