+Open data
-Basic information
Entry | Database: PDB / ID: 6b5v | ||||||
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Title | Structure of TRPV5 in complex with econazole | ||||||
Components | Transient receptor potential cation channel subfamily V member 5 | ||||||
Keywords | MEMBRANE PROTEIN / TRPV5 / Econazole / Transient Receptor Potential Channel / Cryo-EM | ||||||
Function / homology | Function and homology information regulation of urine volume / calcium ion import across plasma membrane / calcium ion homeostasis / calcium ion transmembrane transport / calcium channel activity / calcium ion transport / protein homotetramerization / calmodulin binding / apical plasma membrane / identical protein binding ...regulation of urine volume / calcium ion import across plasma membrane / calcium ion homeostasis / calcium ion transmembrane transport / calcium channel activity / calcium ion transport / protein homotetramerization / calmodulin binding / apical plasma membrane / identical protein binding / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | Oryctolagus cuniculus (rabbit) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.8 Å | ||||||
Authors | Hughes, T.E.T. / Lodowski, D.T. / Huynh, K.W. / Yazici, A. / del Rosario, J. / Kapoor, A. / Basak, S. / Samanta, A. / Chakrapani, S. / Zhou, Z.H. ...Hughes, T.E.T. / Lodowski, D.T. / Huynh, K.W. / Yazici, A. / del Rosario, J. / Kapoor, A. / Basak, S. / Samanta, A. / Chakrapani, S. / Zhou, Z.H. / Filizola, M. / Rohacs, T. / Han, S. / Moiseenkova-Bell, V.Y. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2018 Title: Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM. Authors: Taylor E T Hughes / David T Lodowski / Kevin W Huynh / Aysenur Yazici / John Del Rosario / Abhijeet Kapoor / Sandip Basak / Amrita Samanta / Xu Han / Sudha Chakrapani / Z Hong Zhou / Marta ...Authors: Taylor E T Hughes / David T Lodowski / Kevin W Huynh / Aysenur Yazici / John Del Rosario / Abhijeet Kapoor / Sandip Basak / Amrita Samanta / Xu Han / Sudha Chakrapani / Z Hong Zhou / Marta Filizola / Tibor Rohacs / Seungil Han / Vera Y Moiseenkova-Bell / Abstract: The transient receptor potential vanilloid 5 (TRPV5) channel is a member of the transient receptor potential (TRP) channel family, which is highly selective for Ca, that is present primarily at the ...The transient receptor potential vanilloid 5 (TRPV5) channel is a member of the transient receptor potential (TRP) channel family, which is highly selective for Ca, that is present primarily at the apical membrane of distal tubule epithelial cells in the kidney and plays a key role in Ca reabsorption. Here we present the structure of the full-length rabbit TRPV5 channel as determined using cryo-EM in complex with its inhibitor econazole. This structure reveals that econazole resides in a hydrophobic pocket analogous to that occupied by phosphatidylinositides and vanilloids in TRPV1, thus suggesting conserved mechanisms for ligand recognition and lipid binding among TRPV channels. The econazole-bound TRPV5 structure adopts a closed conformation with a distinct lower gate that occludes Ca permeation through the channel. Structural comparisons between TRPV5 and other TRPV channels, complemented with molecular dynamics (MD) simulations of the econazole-bound TRPV5 structure, allowed us to gain mechanistic insight into TRPV5 channel inhibition by small molecules. | ||||||
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 | 6b5v.cif.gz | 422.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6b5v.ent.gz | 346.2 KB | Display | PDB format |
PDBx/mmJSON format | 6b5v.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6b5v_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 6b5v_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6b5v_validation.xml.gz | 71.4 KB | Display | |
Data in CIF | 6b5v_validation.cif.gz | 104.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/b5/6b5v ftp://data.pdbj.org/pub/pdb/validation_reports/b5/6b5v | HTTPS FTP |
-Related structure data
Related structure data | 7058MC 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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1 |
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-Components
#1: Protein | Mass: 82899.656 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Gene: Trpv5, Ecac1 / Production host: Saccharomyces cerevisiae (brewer's yeast) / Strain (production host): BJ5457 / References: UniProt: Q9XSM3 #2: Chemical | ChemComp-ECL / #3: Chemical | ChemComp-CA / | |
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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: Full-length TRPV5 in complex with econazole / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | |||||||||||||||||||||||||
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Source (natural) | Organism: Oryctolagus cuniculus (rabbit) | |||||||||||||||||||||||||
Source (recombinant) | Organism: Saccharomyces cerevisiae (brewer's yeast) / Strain: BJ5457 | |||||||||||||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 2.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Grid type: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-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 FIELD / Nominal magnification: 45455 X / Cs: 2.7 mm |
Image recording | Average exposure time: 0.2 sec. / Electron dose: 2 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 3313 |
Image scans | Movie frames/image: 50 |
-Processing
Software | Name: PHENIX / Version: dev_2870: / Classification: refinement | ||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 925927 | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 50566 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL / Target criteria: correlation coefficient | ||||||||||||||||||||||||||||||||
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