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Yorodumi- PDB-6dg7: Full-length 5-HT3A receptor in a serotonin-bound conformation- State 1 -
+Open data
-Basic information
Entry | Database: PDB / ID: 6dg7 | ||||||||||||
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Title | Full-length 5-HT3A receptor in a serotonin-bound conformation- State 1 | ||||||||||||
Components | 5-hydroxytryptamine receptor 3A | ||||||||||||
Keywords | MEMBRANE PROTEIN | ||||||||||||
Function / homology | Function and homology information Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / excitatory extracellular ligand-gated monoatomic ion channel activity / serotonin binding / inorganic cation transmembrane transport / cleavage furrow / transmembrane transporter complex / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential ...Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / excitatory extracellular ligand-gated monoatomic ion channel activity / serotonin binding / inorganic cation transmembrane transport / cleavage furrow / transmembrane transporter complex / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / presynaptic membrane / postsynaptic membrane / neuron projection / axon / neuronal cell body / glutamatergic synapse / synapse / identical protein binding / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Mus musculus (house mouse) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.32 Å | ||||||||||||
Authors | Basak, S. / Chakrapani, S. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: Nature / Year: 2018 Title: Cryo-EM reveals two distinct serotonin-bound conformations of full-length 5-HT receptor. Authors: Sandip Basak / Yvonne Gicheru / Shanlin Rao / Mark S P Sansom / Sudha Chakrapani / Abstract: The 5-HT serotonin receptor, a cationic pentameric ligand-gated ion channel (pLGIC), is the clinical target for management of nausea and vomiting associated with radiation and chemotherapies. Upon ...The 5-HT serotonin receptor, a cationic pentameric ligand-gated ion channel (pLGIC), is the clinical target for management of nausea and vomiting associated with radiation and chemotherapies. Upon binding, serotonin induces a global conformational change that encompasses the ligand-binding extracellular domain (ECD), the transmembrane domain (TMD) and the intracellular domain (ICD), the molecular details of which are unclear. Here we present two serotonin-bound structures of the full-length 5-HT receptor in distinct conformations at 3.32 Å and 3.89 Å resolution that reveal the mechanism underlying channel activation. In comparison to the apo 5-HT receptor, serotonin-bound states underwent a large twisting motion in the ECD and TMD, leading to the opening of a 165 Å permeation pathway. Notably, this motion results in the creation of lateral portals for ion permeation at the interface of the TMD and ICD. Combined with molecular dynamics simulations, these structures provide novel insights into conformational coupling across domains and functional modulation. | ||||||||||||
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 | 6dg7.cif.gz | 362.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6dg7.ent.gz | 305.1 KB | Display | PDB format |
PDBx/mmJSON format | 6dg7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6dg7_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 6dg7_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 6dg7_validation.xml.gz | 63 KB | Display | |
Data in CIF | 6dg7_validation.cif.gz | 91.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dg/6dg7 ftp://data.pdbj.org/pub/pdb/validation_reports/dg/6dg7 | HTTPS FTP |
-Related structure data
Related structure data | 7882MC 7883C 6dg8C 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: 52523.660 Da / Num. of mol.: 5 / Fragment: UNP residues 35-489 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Htr3a / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): sf9 / References: UniProt: E9QLC0, UniProt: P23979*PLUS #2: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #3: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #4: Chemical | ChemComp-SRO / #5: Water | ChemComp-HOH / | |
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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: Serotonin receptor / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.27 MDa / Experimental value: NO |
Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) / Strain: sf9 |
Buffer solution | pH: 8 |
Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK I / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: blot for 2.5 seconds |
-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: 130000 X / Cs: 2.7 mm / C2 aperture diameter: 70 µm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 40 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 2810 |
Image scans | Movie frames/image: 40 / Used frames/image: 2-39 |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / 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: 749970 | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C5 (5 fold cyclic) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.32 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 103698 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 154 / Protocol: OTHER / Space: REAL |