+Open data
-Basic information
Entry | Database: PDB / ID: 6djs | |||||||||
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Title | Hybrid model of TRPC3 in GDN | |||||||||
Components | Short transient receptor potential channel 3 | |||||||||
Keywords | TRANSPORT PROTEIN / TRP channel / Ion Channel / Membrane protein / cerebellum / moonwalker | |||||||||
Function / homology | Function and homology information positive regulation of cardiac muscle hypertrophy in response to stress / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / Elevation of cytosolic Ca2+ levels / Effects of PIP2 hydrolysis / cation channel complex / inositol 1,4,5 trisphosphate binding / calcium-activated cation channel activity / TRP channels / positive regulation of calcium ion transport into cytosol ...positive regulation of cardiac muscle hypertrophy in response to stress / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / Elevation of cytosolic Ca2+ levels / Effects of PIP2 hydrolysis / cation channel complex / inositol 1,4,5 trisphosphate binding / calcium-activated cation channel activity / TRP channels / positive regulation of calcium ion transport into cytosol / response to ATP / phototransduction / single fertilization / MECP2 regulates neuronal receptors and channels / regulation of cytosolic calcium ion concentration / calcium ion transmembrane transport / calcium channel activity / response to calcium ion / calcium ion transport / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5.8 Å | |||||||||
Authors | Sierra-Valdez, F.J. / Azumaya, C.M. / Nakagawa, T. / Cordero-Morales, J.F. | |||||||||
Funding support | United States, 2items
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Citation | Journal: J Biol Chem / Year: 2018 Title: Structure-function analyses of the ion channel TRPC3 reveal that its cytoplasmic domain allosterically modulates channel gating. Authors: Francisco Sierra-Valdez / Caleigh M Azumaya / Luis O Romero / Terunaga Nakagawa / Julio F Cordero-Morales / Abstract: The transient receptor potential ion channels support Ca permeation in many organs, including the heart, brain, and kidney. Genetic mutations in transient receptor potential cation channel subfamily ...The transient receptor potential ion channels support Ca permeation in many organs, including the heart, brain, and kidney. Genetic mutations in transient receptor potential cation channel subfamily C member 3 (TRPC3) are associated with neurodegenerative diseases, memory loss, and hypertension. To better understand the conformational changes that regulate TRPC3 function, we solved the cryo-EM structures for the full-length human TRPC3 and its cytoplasmic domain (CPD) in the apo state at 5.8- and 4.0-Å resolution, respectively. These structures revealed that the TRPC3 transmembrane domain resembles those of other TRP channels and that the CPD is a stable module involved in channel assembly and gating. We observed the presence of a C-terminal domain swap at the center of the CPD where horizontal helices (HHs) transition into a coiled-coil bundle. Comparison of TRPC3 structures revealed that the HHs can reside in two distinct positions. Electrophysiological analyses disclosed that shortening the length of the C-terminal loop connecting the HH with the TRP helices increases TRPC3 activity and that elongating the length of the loop has the opposite effect. Our findings indicate that the C-terminal loop affects channel gating by altering the allosteric coupling between the cytoplasmic and transmembrane domains. We propose that molecules that target the HH may represent a promising strategy for controlling TRPC3-associated neurological disorders and hypertension. | |||||||||
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 | 6djs.cif.gz | 292 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6djs.ent.gz | 236.9 KB | Display | PDB format |
PDBx/mmJSON format | 6djs.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dj/6djs ftp://data.pdbj.org/pub/pdb/validation_reports/dj/6djs | HTTPS FTP |
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-Related structure data
Related structure data | 7940MC 7823C 6d7lC 6djrC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 68783.977 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TRPC3, TRP3 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q13507 |
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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: Homotetramer of human TRPC3 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | ||||||||||||||||||||
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Molecular weight | Value: 0.97 MDa / Experimental value: YES | ||||||||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) | ||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Monodisperse | ||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid type: C-flat-2/1 | ||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Tecnai Polara / Image courtesy: FEI Company |
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Microscopy | Model: FEI POLARA 300 |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 31000 X |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 100 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||
3D reconstruction | Resolution: 5.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 56291 / Symmetry type: POINT | ||||||||||||
Atomic model building | B value: 400 / Protocol: OTHER / Space: REAL Details: Hybrid model of 6DJR and 6CV9 (cytoplasmic domain of TRPC6 with amino acids mutated that differ between TRPC6 and TRPC3) |