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- PDB-8ear: Structure of the full-length IP3R1 channel determined in the pres... -
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Basic information
Entry | Database: PDB / ID: 8ear | ||||||||||||||||||||||||
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Title | Structure of the full-length IP3R1 channel determined in the presence of Calcium/IP3/ATP | ||||||||||||||||||||||||
![]() | Inositol 1,4,5-trisphosphate receptor type 1 | ||||||||||||||||||||||||
![]() | MEMBRANE PROTEIN / Calcium channel / lipid nanodisc | ||||||||||||||||||||||||
Function / homology | ![]() Effects of PIP2 hydrolysis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / inositol 1,4,5-trisphosphate receptor activity involved in regulation of postsynaptic cytosolic calcium levels / Elevation of cytosolic Ca2+ levels / cGMP effects / smooth endoplasmic reticulum membrane / platelet dense tubular network / negative regulation of calcium-mediated signaling / calcineurin complex / platelet dense granule membrane ...Effects of PIP2 hydrolysis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / inositol 1,4,5-trisphosphate receptor activity involved in regulation of postsynaptic cytosolic calcium levels / Elevation of cytosolic Ca2+ levels / cGMP effects / smooth endoplasmic reticulum membrane / platelet dense tubular network / negative regulation of calcium-mediated signaling / calcineurin complex / platelet dense granule membrane / epithelial fluid transport / ion channel modulating, G protein-coupled receptor signaling pathway / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / regulation of postsynaptic cytosolic calcium ion concentration / inositol 1,4,5-trisphosphate-gated calcium channel activity / voluntary musculoskeletal movement / inositol 1,4,5 trisphosphate binding / positive regulation of calcium ion transport / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / endoplasmic reticulum calcium ion homeostasis / positive regulation of hepatocyte proliferation / nuclear inner membrane / transport vesicle membrane / Ion homeostasis / dendrite development / intracellularly gated calcium channel activity / ligand-gated ion channel signaling pathway / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / GABA-ergic synapse / calcium channel inhibitor activity / cellular response to cAMP / release of sequestered calcium ion into cytosol / phosphatidylinositol binding / post-embryonic development / secretory granule membrane / synaptic membrane / sarcoplasmic reticulum / liver regeneration / calcium-mediated signaling / calcium ion transmembrane transport / Schaffer collateral - CA1 synapse / cell morphogenesis / positive regulation of insulin secretion / positive regulation of neuron projection development / calcium ion transport / presynapse / nuclear envelope / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cellular response to hypoxia / postsynapse / protein phosphatase binding / transmembrane transporter binding / postsynaptic density / response to hypoxia / positive regulation of apoptotic process / protein domain specific binding / neuronal cell body / synapse / calcium ion binding / dendrite / protein-containing complex binding / endoplasmic reticulum membrane / nucleolus / negative regulation of apoptotic process / perinuclear region of cytoplasm / endoplasmic reticulum / protein-containing complex / identical protein binding / membrane / plasma membrane / cytoplasm Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||||||||||||||
![]() | Fan, G. / Baker, M.R. / Terry, L.E. / Arige, V. / Chen, M. / Seryshev, A.B. / Baker, M.L. / Ludtke, S.J. / Yule, D.I. / Serysheva, I.I. | ||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Conformational motions and ligand-binding underlying gating and regulation in IPR channel. Authors: Guizhen Fan / Mariah R Baker / Lara E Terry / Vikas Arige / Muyuan Chen / Alexander B Seryshev / Matthew L Baker / Steven J Ludtke / David I Yule / Irina I Serysheva / ![]() Abstract: Inositol-1,4,5-trisphosphate receptors (IPRs) are activated by IP and Ca and their gating is regulated by various intracellular messengers that finely tune the channel activity. Here, using single ...Inositol-1,4,5-trisphosphate receptors (IPRs) are activated by IP and Ca and their gating is regulated by various intracellular messengers that finely tune the channel activity. Here, using single particle cryo-EM analysis we determined 3D structures of the nanodisc-reconstituted IPR1 channel in two ligand-bound states. These structures provide unprecedented details governing binding of IP, Ca and ATP, revealing conformational changes that couple ligand-binding to channel opening. Using a deep-learning approach and 3D variability analysis we extracted molecular motions of the key protein domains from cryo-EM density data. We find that IP binding relies upon intrinsic flexibility of the ARM2 domain in the tetrameric channel. Our results highlight a key role of dynamic side chains in regulating gating behavior of IPR channels. This work represents a stepping-stone to developing mechanistic understanding of conformational pathways underlying ligand-binding, activation and regulation of the channel. | ||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 1.7 MB | Display | ![]() |
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PDB format | ![]() | 1.4 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.7 MB | Display | ![]() |
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Full document | ![]() | 2.9 MB | Display | |
Data in XML | ![]() | 262.2 KB | Display | |
Data in CIF | ![]() | 385.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 27983MC ![]() 8eaqC M: map data used to model this data C: citing same article ( |
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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
-Protein , 1 types, 4 molecules ABCD
#1: Protein | Mass: 313657.406 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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-Non-polymers , 5 types, 56 molecules ![](data/chem/img/ZN.gif)
![](data/chem/img/ATP.gif)
![](data/chem/img/I3P.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/PLX.gif)
![](data/chem/img/ATP.gif)
![](data/chem/img/I3P.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/PLX.gif)
#2: Chemical | ChemComp-ZN / #3: Chemical | ChemComp-ATP / #4: Chemical | ChemComp-I3P / #5: Chemical | ChemComp-CA / #6: Chemical | ChemComp-PLX / ( |
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-Details
Has ligand of interest | Y |
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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 |
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Sample preparation
Component | Name: Type 1 inositol 1,4,5-trisphosphate receptor tetrameric protein complex Type: COMPLEX / Entity ID: #1 / Source: NATURAL |
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Molecular weight | Value: 1.3 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: reconstituted in lipid nanodisc |
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/1 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Calibrated magnification: 46943 X / Nominal defocus max: 2500 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 0.2 sec. / Electron dose: 49 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Num. of real images: 24478 |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
Image scans | Sampling size: 5 µm / Width: 3840 / Height: 3712 / Movie frames/image: 35 |
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Processing
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EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1452797 / Details: NeuralNet autopicking in EMAN2 | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 133740 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7LHE | ||||||||||||||||||||||||||||||||||||
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