+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0225 | |||||||||
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Title | Mouse serotonin 5-HT3 receptor, serotonin-bound, F conformation | |||||||||
Map data | Mouse serotonin 5-HT3 receptor, serotonin-bound, F conformation | |||||||||
Sample |
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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 / serotonin binding / inorganic cation transmembrane transport / excitatory extracellular ligand-gated monoatomic ion channel activity / 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 / serotonin binding / inorganic cation transmembrane transport / excitatory extracellular ligand-gated monoatomic ion channel activity / 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 | single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
Authors | Polovinkin L / Neumann E / Schoehn G / Nury H | |||||||||
Citation | Journal: Nature / Year: 2018 Title: Conformational transitions of the serotonin 5-HT receptor. Authors: Lucie Polovinkin / Ghérici Hassaine / Jonathan Perot / Emmanuelle Neumann / Anders A Jensen / Solène N Lefebvre / Pierre-Jean Corringer / Jacques Neyton / Christophe Chipot / Francois ...Authors: Lucie Polovinkin / Ghérici Hassaine / Jonathan Perot / Emmanuelle Neumann / Anders A Jensen / Solène N Lefebvre / Pierre-Jean Corringer / Jacques Neyton / Christophe Chipot / Francois Dehez / Guy Schoehn / Hugues Nury / Abstract: The serotonin 5-HT receptor is a pentameric ligand-gated ion channel (pLGIC). It belongs to a large family of receptors that function as allosteric signal transducers across the plasma membrane; upon ...The serotonin 5-HT receptor is a pentameric ligand-gated ion channel (pLGIC). It belongs to a large family of receptors that function as allosteric signal transducers across the plasma membrane; upon binding of neurotransmitter molecules to extracellular sites, the receptors undergo complex conformational transitions that result in transient opening of a pore permeable to ions. 5-HT receptors are therapeutic targets for emesis and nausea, irritable bowel syndrome and depression. In spite of several reported pLGIC structures, no clear unifying view has emerged on the conformational transitions involved in channel gating. Here we report four cryo-electron microscopy structures of the full-length mouse 5-HT receptor in complex with the anti-emetic drug tropisetron, with serotonin, and with serotonin and a positive allosteric modulator, at resolutions ranging from 3.2 Å to 4.5 Å. The tropisetron-bound structure resembles those obtained with an inhibitory nanobody or without ligand. The other structures include an 'open' state and two ligand-bound states. We present computational insights into the dynamics of the structures, their pore hydration and free-energy profiles, and characterize movements at the gate level and cation accessibility in the pore. Together, these data deepen our understanding of the gating mechanism of pLGICs and capture ligand binding in unprecedented detail. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_0225.map.gz | 42.1 MB | EMDB map data format | |
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Header (meta data) | emd-0225-v30.xml emd-0225.xml | 10.6 KB 10.6 KB | Display Display | EMDB header |
Images | emd_0225.png | 47.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0225 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0225 | HTTPS FTP |
-Validation report
Summary document | emd_0225_validation.pdf.gz | 341.9 KB | Display | EMDB validaton report |
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Full document | emd_0225_full_validation.pdf.gz | 341.5 KB | Display | |
Data in XML | emd_0225_validation.xml.gz | 6.2 KB | Display | |
Data in CIF | emd_0225_validation.cif.gz | 7.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0225 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0225 | HTTPS FTP |
-Related structure data
Related structure data | 6hinMC 0226C 0227C 0228C 6hioC 6hiqC 6hisC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_0225.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Mouse serotonin 5-HT3 receptor, serotonin-bound, F conformation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.039 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : 5-HT3 receptor, serotonin-bound
Entire | Name: 5-HT3 receptor, serotonin-bound |
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Components |
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-Supramolecule #1: 5-HT3 receptor, serotonin-bound
Supramolecule | Name: 5-HT3 receptor, serotonin-bound / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK 293 |
-Macromolecule #1: 5-hydroxytryptamine receptor 3A
Macromolecule | Name: 5-hydroxytryptamine receptor 3A / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 51.906031 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: PALLRLSDHL LANYKKGVRP VRDWRKPTTV SIDVIMYAIL NVDEKNQVLT TYIWYRQYWT DEFLQWTPED FDNVTKLSIP TDSIWVPDI LINEFVDVGK SPNIPYVYVH HRGEVQNYKP LQLVTACSLD IYNFPFDVQN CSLTFTSWLH TIQDINITLW R SPEEVRSD ...String: PALLRLSDHL LANYKKGVRP VRDWRKPTTV SIDVIMYAIL NVDEKNQVLT TYIWYRQYWT DEFLQWTPED FDNVTKLSIP TDSIWVPDI LINEFVDVGK SPNIPYVYVH HRGEVQNYKP LQLVTACSLD IYNFPFDVQN CSLTFTSWLH TIQDINITLW R SPEEVRSD KSIFINQGEW ELLEVFPQFK EFSIDISNSY AEMKFYVIIR RRPLFYAVSL LLPSIFLMVV DIVGFCLPPD SG ERVSFKI TLLLGYSVFL IIVSDTLPAT AIGTPLIGVY FVVCMALLVI SLAETIFIVR LVHKQDLQRP VPDWLRHLVL DRI AWILCL GEQPMAHRPP ATFQANKTDD CSGSDLLPAM GNHCSHVGGP QDLEKTPRGR GSPLPPPREA SLAVRGLLQE LSSI RHFLE KRDEMREVAR DWLRVGYVLD RLLFRIYLLA VLAYSITLVT LWSIW |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 5 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #4: SEROTONIN
Macromolecule | Name: SEROTONIN / type: ligand / ID: 4 / Number of copies: 5 / Formula: SRO |
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Molecular weight | Theoretical: 176.215 Da |
Chemical component information | ChemComp-SRO: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Applied symmetry - Point group: C5 (5 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 10667 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |