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- PDB-8dtb: Focus/local refined map in C1 of signal subtracted RyR1 particles... -
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Basic information
Entry | Database: PDB / ID: 8dtb | |||||||||
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Title | Focus/local refined map in C1 of signal subtracted RyR1 particles in complex with ImperaCalcin | |||||||||
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![]() | TOXIN / ryanodine receptor / ion channel / snake toxin / calcin / complex / membrane protein | |||||||||
Function / homology | ![]() ATP-gated ion channel activity / terminal cisterna / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / ossification involved in bone maturation / skin development / organelle membrane / cellular response to caffeine / outflow tract morphogenesis ...ATP-gated ion channel activity / terminal cisterna / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / ossification involved in bone maturation / skin development / organelle membrane / cellular response to caffeine / outflow tract morphogenesis / intracellularly gated calcium channel activity / toxic substance binding / smooth endoplasmic reticulum / voltage-gated calcium channel activity / calcium channel inhibitor activity / skeletal muscle fiber development / striated muscle contraction / muscle contraction / release of sequestered calcium ion into cytosol / sarcoplasmic reticulum membrane / cellular response to calcium ion / sarcoplasmic reticulum / calcium ion transmembrane transport / calcium channel activity / sarcolemma / Z disc / intracellular calcium ion homeostasis / disordered domain specific binding / protein homotetramerization / toxin activity / transmembrane transporter binding / calmodulin binding / calcium ion binding / extracellular region / ATP binding / identical protein binding / membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.14 Å | |||||||||
![]() | Haji-Ghassemi, O. / Van Petegm, F. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM analysis of scorpion toxin binding to Ryanodine Receptors reveals subconductance that is abolished by PKA phosphorylation. Authors: Omid Haji-Ghassemi / Yu Seby Chen / Kellie Woll / Georgina B Gurrola / Carmen R Valdivia / Wenxuan Cai / Songhua Li / Hector H Valdivia / Filip Van Petegem / ![]() ![]() ![]() ![]() Abstract: Calcins are peptides from scorpion venom with the unique ability to cross cell membranes, gaining access to intracellular targets. Ryanodine Receptors (RyR) are intracellular ion channels that ...Calcins are peptides from scorpion venom with the unique ability to cross cell membranes, gaining access to intracellular targets. Ryanodine Receptors (RyR) are intracellular ion channels that control release of Ca from the endoplasmic and sarcoplasmic reticulum. Calcins target RyRs and induce long-lived subconductance states, whereby single-channel currents are decreased. We used cryo-electron microscopy to reveal the binding and structural effects of imperacalcin, showing that it opens the channel pore and causes large asymmetry throughout the cytosolic assembly of the tetrameric RyR. This also creates multiple extended ion conduction pathways beyond the transmembrane region, resulting in subconductance. Phosphorylation of imperacalcin by protein kinase A prevents its binding to RyR through direct steric hindrance, showing how posttranslational modifications made by the host organism can determine the fate of a natural toxin. The structure provides a direct template for developing calcin analogs that result in full channel block, with potential to treat RyR-related disorders. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 639.7 KB | Display | ![]() |
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PDB format | ![]() | 347.3 KB | 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 | ![]() 27695MC ![]() 8drpC ![]() 8dujC ![]() 8dveC C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein/peptide | Mass: 3776.495 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() | ||||||
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#2: Protein | Mass: 565908.625 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #3: Chemical | ChemComp-ATP / #4: Chemical | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: RyR1 in complex with ImperaCalcin / Type: COMPLEX / Entity ID: #1-#2 / Source: MULTIPLE SOURCES | ||||||||||||
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Molecular weight | Value: 2.2 MDa / Experimental value: YES | ||||||||||||
Source (natural) |
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Buffer solution | pH: 7.4 | ||||||||||||
Specimen | Conc.: 10 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R2/2 | ||||||||||||
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 / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm |
Image recording | Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON III (4k x 4k) |
Image scans | Width: 4096 / Height: 4096 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.14 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 307078 / Algorithm: FOURIER SPACE / Num. of class averages: 3 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL | |||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6M2W Accession code: 6M2W / Source name: PDB / Type: experimental model | |||||||||||||||||||||||||||||||||||||||||||||
Refinement | Highest resolution: 3.14 Å |