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Open data
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Basic information
Entry | Database: PDB / ID: 6dmw | |||||||||
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Title | Calmodulin-bound full-length rbTRPV5 | |||||||||
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![]() | TRANSPORT PROTEIN / calmodulin / TRPV5 / full-length / calcium channel | |||||||||
Function / homology | ![]() establishment of protein localization to mitochondrial membrane / type 3 metabotropic glutamate receptor binding / regulation of urine volume / establishment of protein localization to membrane / presynaptic cytosol / regulation of synaptic vesicle endocytosis / organelle localization by membrane tethering / regulation of synaptic vesicle exocytosis / postsynaptic cytosol / mitochondrion-endoplasmic reticulum membrane tethering ...establishment of protein localization to mitochondrial membrane / type 3 metabotropic glutamate receptor binding / regulation of urine volume / establishment of protein localization to membrane / presynaptic cytosol / regulation of synaptic vesicle endocytosis / organelle localization by membrane tethering / regulation of synaptic vesicle exocytosis / postsynaptic cytosol / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / regulation of cardiac muscle cell action potential / nitric-oxide synthase binding / negative regulation of ryanodine-sensitive calcium-release channel activity / protein phosphatase activator activity / calcium ion import across plasma membrane / adenylate cyclase binding / catalytic complex / detection of calcium ion / regulation of cardiac muscle contraction / calcium channel regulator activity / regulation of ryanodine-sensitive calcium-release channel activity / cellular response to interferon-beta / calcium channel inhibitor activity / phosphatidylinositol 3-kinase binding / calcium ion homeostasis / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / : / titin binding / voltage-gated potassium channel complex / sperm midpiece / calcium channel complex / response to amphetamine / adenylate cyclase activator activity / nitric-oxide synthase regulator activity / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / regulation of cytokinesis / spindle microtubule / calcium ion transmembrane transport / positive regulation of receptor signaling pathway via JAK-STAT / Schaffer collateral - CA1 synapse / calcium channel activity / cellular response to type II interferon / spindle pole / response to calcium ion / calcium-dependent protein binding / G2/M transition of mitotic cell cycle / calcium ion transport / myelin sheath / growth cone / protein homotetramerization / transmembrane transporter binding / calmodulin binding / apical plasma membrane / protein domain specific binding / centrosome / calcium ion binding / protein kinase binding / protein-containing complex / mitochondrion / nucleoplasm / identical protein binding / metal ion binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.4 Å | |||||||||
![]() | Hughes, T.E.T. / Pumroy, R.A. / Moiseenkova-Bell, V.Y. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights on TRPV5 gating by endogenous modulators. Authors: Taylor E T Hughes / Ruth A Pumroy / Aysenur Torun Yazici / Marina A Kasimova / Edwin C Fluck / Kevin W Huynh / Amrita Samanta / Sudheer K Molugu / Z Hong Zhou / Vincenzo Carnevale / Tibor ...Authors: Taylor E T Hughes / Ruth A Pumroy / Aysenur Torun Yazici / Marina A Kasimova / Edwin C Fluck / Kevin W Huynh / Amrita Samanta / Sudheer K Molugu / Z Hong Zhou / Vincenzo Carnevale / Tibor Rohacs / Vera Y Moiseenkova-Bell / ![]() Abstract: TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5- ...TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P and CaM. The PI(4,5)P structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-π interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery. | |||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 453.3 KB | Display | ![]() |
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PDB format | ![]() | 372.1 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 | ![]() 7967MC ![]() 7965C ![]() 7966C ![]() 6dmrC ![]() 6dmuC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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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.) ![]() ![]() ![]() ![]() #2: Protein | | Mass: 16852.545 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #3: Chemical | |
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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
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Buffer solution | pH: 8.8 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Details: unspecified | ||||||||||||||||||||||||
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: 1 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 47484 / Symmetry type: POINT |