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- PDB-8j1f: GSK101 bound state of mTRPV4 -

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Basic information

Entry
Database: PDB / ID: 8j1f
TitleGSK101 bound state of mTRPV4
ComponentsTransient receptor potential cation channel subfamily V member 4
KeywordsMEMBRANE PROTEIN / mTRPV4 / STRUCTURAL PROTEIN
Function / homology
Function and homology information


stretch-activated, monoatomic cation-selective, calcium channel activity / blood vessel endothelial cell delamination / regulation of response to osmotic stress / osmosensor activity / vasopressin secretion / positive regulation of striated muscle contraction / calcium ion import into cytosol / negative regulation of brown fat cell differentiation / positive regulation of microtubule depolymerization / positive regulation of macrophage inflammatory protein 1 alpha production ...stretch-activated, monoatomic cation-selective, calcium channel activity / blood vessel endothelial cell delamination / regulation of response to osmotic stress / osmosensor activity / vasopressin secretion / positive regulation of striated muscle contraction / calcium ion import into cytosol / negative regulation of brown fat cell differentiation / positive regulation of microtubule depolymerization / positive regulation of macrophage inflammatory protein 1 alpha production / hyperosmotic salinity response / positive regulation of chemokine (C-X-C motif) ligand 1 production / positive regulation of chemokine (C-C motif) ligand 5 production / cartilage development involved in endochondral bone morphogenesis / cellular hypotonic salinity response / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / cellular hypotonic response / cortical microtubule organization / TRP channels / multicellular organismal-level water homeostasis / positive regulation of vascular permeability / osmosensory signaling pathway / cell-cell junction assembly / positive regulation of monocyte chemotactic protein-1 production / calcium ion import / cellular response to osmotic stress / response to osmotic stress / regulation of aerobic respiration / cortical actin cytoskeleton / diet induced thermogenesis / positive regulation of macrophage chemotaxis / microtubule polymerization / alpha-tubulin binding / beta-tubulin binding / monoatomic cation channel activity / energy homeostasis / cytoplasmic microtubule / SH2 domain binding / protein kinase C binding / actin filament organization / positive regulation of JNK cascade / filopodium / adherens junction / response to insulin / positive regulation of interleukin-6 production / calcium channel activity / ruffle membrane / intracellular calcium ion homeostasis / positive regulation of inflammatory response / actin filament binding / glucose homeostasis / lamellipodium / negative regulation of neuron projection development / cellular response to heat / positive regulation of cytosolic calcium ion concentration / growth cone / microtubule binding / calmodulin binding / response to hypoxia / positive regulation of ERK1 and ERK2 cascade / cilium / apical plasma membrane / focal adhesion / lipid binding / positive regulation of gene expression / protein kinase binding / cell surface / negative regulation of transcription by RNA polymerase II / ATP binding / metal ion binding / identical protein binding / plasma membrane
Similarity search - Function
Transient receptor potential cation channel subfamily V member 4 / Transient receptor potential cation channel subfamily V member 1-4 / Transient receptor potential cation channel subfamily V / Ankyrin repeat / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Chem-XQ3 / Transient receptor potential cation channel subfamily V member 4
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.62 Å
AuthorsZhen, W.X. / Yang, F.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32122040 China
CitationJournal: Cell Discov / Year: 2023
Title: Structural basis of ligand activation and inhibition in a mammalian TRPV4 ion channel.
Authors: Wenxuan Zhen / Zhijun Zhao / Shenghai Chang / Xiaoying Chen / Yangzhuoqun Wan / Fan Yang /
History
DepositionApr 12, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Aug 9, 2023Provider: repository / Type: Initial release
Revision 1.1May 29, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Transient receptor potential cation channel subfamily V member 4
B: Transient receptor potential cation channel subfamily V member 4
C: Transient receptor potential cation channel subfamily V member 4
D: Transient receptor potential cation channel subfamily V member 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)321,0698
Polymers318,4474
Non-polymers2,6224
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein
Transient receptor potential cation channel subfamily V member 4 / TrpV4 / Osm-9-like TRP channel 4 / OTRPC4 / Transient receptor potential protein 12 / TRP12 / ...TrpV4 / Osm-9-like TRP channel 4 / OTRPC4 / Transient receptor potential protein 12 / TRP12 / Vanilloid receptor-like channel 2 / Vanilloid receptor-like protein 2 / Vanilloid receptor-related osmotically-activated channel / VR-OAC


Mass: 79611.680 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Trpv4, Trp12, Vrl2, Vroac / Production host: Homo sapiens (human) / References: UniProt: Q9EPK8
#2: Chemical
ChemComp-XQ3 / N-[(2S)-1-{4-[N-(2,4-dichlorobenzene-1-sulfonyl)-L-seryl]piperazin-1-yl}-4-methyl-1-oxopentan-2-yl]-1-benzothiophene-2-carboxamide / GSK1016790A


Mass: 655.613 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C28H32Cl2N4O6S2
Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: GSK101 bound state of mTRPV4 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Mus musculus (house mouse)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
SpecimenConc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1600 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 52 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.62 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 452263 / Symmetry type: POINT

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