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Open data
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Basic information
Entry | Database: PDB / ID: 6jhn | ||||||
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Title | Structure of RyR2 (F/C/Ca2+ dataset) | ||||||
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Function / homology | ![]() positive regulation of sequestering of calcium ion / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Chi, X.M. / Gong, D.S. / Ren, K. / Zhou, G.W. / Huang, G.X.Y. / Lei, J.L. / Zhou, Q. / Yan, N. | ||||||
![]() | ![]() 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. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 2.4 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 9826MC ![]() 9823C ![]() 9824C ![]() 9825C ![]() 6jg3C ![]() 6jgzC ![]() 6jh6C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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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) ![]() ![]() ![]() #2: Protein | Mass: 11798.501 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() #3: Chemical | ChemComp-ZN / #4: Chemical | ChemComp-CA / #5: Chemical | ChemComp-CFF / ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: RyR2 in complex with FKBP12.6![]() |
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Source (natural) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Vitrification![]() | Cryogen name: ETHANE |
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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![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
3D reconstruction![]() | Resolution: 4.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 77339 / Symmetry type: POINT |