+
Open data
-
Basic information
Entry | Database: PDB / ID: 8seu | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM Structure of RyR1 (Local Refinement of TMD) | |||||||||
![]() | Ryanodine receptor 1 | |||||||||
![]() | TRANSPORT PROTEIN / Calcium ion channel / skeletal muscle / nucleotide / homotetramer | |||||||||
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 / 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 / transmembrane transporter binding / calmodulin binding / calcium ion binding / ATP binding / identical protein binding / membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | |||||||||
![]() | Cholak, S. / Saville, J.W. / Zhu, X. / Berezuk, A.M. / Tuttle, K.S. / Haji-Ghassemi, O. / Van Petegem, F. / Subramaniam, S. | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Allosteric modulation of ryanodine receptor RyR1 by nucleotide derivatives. Authors: Spencer Cholak / James W Saville / Xing Zhu / Alison M Berezuk / Katharine S Tuttle / Omid Haji-Ghassemi / Francisco J Alvarado / Filip Van Petegem / Sriram Subramaniam / ![]() ![]() Abstract: The coordinated release of Ca from the sarcoplasmic reticulum (SR) is critical for excitation-contraction coupling. This release is facilitated by ryanodine receptors (RyRs) that are embedded in the ...The coordinated release of Ca from the sarcoplasmic reticulum (SR) is critical for excitation-contraction coupling. This release is facilitated by ryanodine receptors (RyRs) that are embedded in the SR membrane. In skeletal muscle, activity of RyR1 is regulated by metabolites such as ATP, which upon binding increase channel open probability (P). To obtain structural insights into the mechanism of RyR1 priming by ATP, we determined several cryo-EM structures of RyR1 bound individually to ATP-γ-S, ADP, AMP, adenosine, adenine, and cAMP. We demonstrate that adenine and adenosine bind RyR1, but AMP is the smallest ATP derivative capable of inducing long-range (>170 Å) structural rearrangements associated with channel activation, establishing a structural basis for key binding site interactions that are the threshold for triggering quaternary structural changes. Our finding that cAMP also induces these structural changes and results in increased channel opening suggests its potential role as an endogenous modulator of RyR1 conductance. | |||||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 725.7 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 438 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 40429MC ![]() 8senC ![]() 8seoC ![]() 8sepC ![]() 8seqC ![]() 8serC ![]() 8sesC ![]() 8setC ![]() 8sevC ![]() 8sewC ![]() 8sexC ![]() 8seyC ![]() 8sezC ![]() 8sf0C M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 565908.625 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #2: Chemical | ChemComp-ZN / Has ligand of interest | N | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: RyR1 in complex with FKBP12.6 / Type: COMPLEX / Entity ID: #1 / Source: MULTIPLE SOURCES |
---|---|
Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | 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 R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 283.15 K |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 96000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-
Processing
EM software | Name: EPU / Version: 3.3 / Category: image acquisition |
---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 45876 / Symmetry type: POINT |