+Open data
-Basic information
Entry | Database: PDB / ID: 6jg3 | ||||||
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Title | Cryo-EM structure of RyR2 (Ca2+ alone dataset) | ||||||
Components | Ryanodine receptor 2 | ||||||
Keywords | MEMBRANE PROTEIN | ||||||
Biological species | Sus scrofa (pig) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.1 Å | ||||||
Authors | Chi, X.M. / Gong, D.S. / Ren, K. / Zhou, G.W. / Huang, G.X.Y. / Lei, J.L. / Zhou, Q. / Yan, N. | ||||||
Citation | Journal: Proc Natl Acad Sci U S A / Year: 2019 Title: Molecular basis for allosteric regulation of the type 2 ryanodine receptor channel gating by key modulators. Authors: Ximin Chi / Deshun Gong / Kang Ren / Gewei Zhou / Gaoxingyu Huang / Jianlin Lei / Qiang Zhou / Nieng Yan / Abstract: The type 2 ryanodine receptor (RyR2) is responsible for releasing Ca from the sarcoplasmic reticulum of cardiomyocytes, subsequently leading to muscle contraction. Here, we report 4 cryo-electron ...The type 2 ryanodine receptor (RyR2) is responsible for releasing Ca from the sarcoplasmic reticulum of cardiomyocytes, subsequently leading to muscle contraction. Here, we report 4 cryo-electron microscopy (cryo-EM) structures of porcine RyR2 bound to distinct modulators that, together with our published structures, provide mechanistic insight into RyR2 regulation. Ca alone induces a contraction of the central domain that facilitates the dilation of the S6 bundle but is insufficient to open the pore. The small-molecule agonist PCB95 helps Ca to overcome the barrier for opening. FKBP12.6 induces a relaxation of the central domain that decouples it from the S6 bundle, stabilizing RyR2 in a closed state even in the presence of Ca and PCB95. Although the channel is open when PCB95 is replaced by caffeine and adenosine 5'-triphosphate (ATP), neither of the modulators alone can sufficiently counter the antagonistic effect to open the channel. Our study marks an important step toward mechanistic understanding of the sophisticated regulation of this key channel whose aberrant activity engenders life-threatening cardiac disorders. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6jg3.cif.gz | 2.4 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6jg3.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6jg3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jg/6jg3 ftp://data.pdbj.org/pub/pdb/validation_reports/jg/6jg3 | HTTPS FTP |
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-Related structure data
Related structure data | 9823MC 9824C 9825C 9826C 6jgzC 6jh6C 6jhnC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 564905.625 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Sus scrofa (pig) #2: Chemical | ChemComp-ZN / |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: homotetramerTetrameric protein / Type: COMPLEX / Entity ID: #1 / Source: NATURAL |
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Source (natural) | Organism: Sus scrofa (pig) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 48.6 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||
3D reconstruction | Resolution: 6.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 24250 / Symmetry type: POINT |