+Open data
-Basic information
Entry | Database: PDB / ID: 6djr | |||||||||
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Title | Full-length human TRPC3 in GDN | |||||||||
Components | Transient Receptor Potential Cation Channel Subfamily C Member 3 | |||||||||
Keywords | TRANSPORT PROTEIN / TRP channel / Ion Channel / Membrane protein / cerebellum / moonwalker | |||||||||
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 | 6djr.cif.gz | 204.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6djr.ent.gz | 175.1 KB | Display | PDB format |
PDBx/mmJSON format | 6djr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6djr_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 6djr_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 6djr_validation.xml.gz | 36.8 KB | Display | |
Data in CIF | 6djr_validation.cif.gz | 65.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dj/6djr ftp://data.pdbj.org/pub/pdb/validation_reports/dj/6djr | HTTPS FTP |
-Related structure data
Related structure data | 7940MC 7823C 6d7lC 6djsC 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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-Components
#1: Protein | Mass: 41719.434 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm) Sequence details | The authors state that the residues could not be assigned at their resolution so all residues are ...The authors state that the residues could not be assigned at their resolution so all residues are modeled as unknown residues. The Short transient receptor potential channel 3 sequence is GAMGSMEGSP | |
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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: TRPC3 homotetramer / 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 mesh size: 200 divisions/in. / 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 FIELD / Nominal magnification: 31000 X |
Specimen holder | Cryogen: NITROGEN |
Image recording | Average exposure time: 8 sec. / Electron dose: 100 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 7 / Num. of real images: 5195 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1410103 | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 5.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 56291 / Num. of class averages: 4 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |