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- EMDB-0228: Mouse serotonin 5-HT3 receptor, tropisetron-bound, T conformation -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-0228 | |||||||||
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Title | Mouse serotonin 5-HT3 receptor, tropisetron-bound, T conformation | |||||||||
![]() | Mouse serotonin 5-HT3 receptor, tropisetron-bound, T conformation | |||||||||
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Function / homology | ![]() Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Polovinkin L / Neumann E / Schoehn G / Nury H | |||||||||
![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 5.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11 KB 11 KB | Display Display | ![]() |
Images | ![]() | 56.6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6hisMC ![]() 0225C ![]() 0226C ![]() 0227C ![]() 6hinC ![]() 6hioC ![]() 6hiqC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Mouse serotonin 5-HT3 receptor, tropisetron-bound, T conformation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
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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: ![]() ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-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: ![]() ![]() ![]() |
Molecular weight | Theoretical: 51.949055 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: TQPALLRLSD HLLANYKKGV RPVRDWRKPT TVSIDVIMYA ILNVDEKNQV LTTYIWYRQY WTDEFLQWTP EDFDNVTKLS IPTDSIWVP DILINEFVDV GKSPNIPYVY VHHRGEVQNY KPLQLVTACS LDIYNFPFDV QNCSLTFTSW LHTIQDINIT L WRSPEEVR ...String: TQPALLRLSD HLLANYKKGV RPVRDWRKPT TVSIDVIMYA ILNVDEKNQV LTTYIWYRQY WTDEFLQWTP EDFDNVTKLS IPTDSIWVP DILINEFVDV GKSPNIPYVY VHHRGEVQNY KPLQLVTACS LDIYNFPFDV QNCSLTFTSW LHTIQDINIT L WRSPEEVR SDKSIFINQG EWELLEVFPQ FKEFSIDISN SYAEMKFYVI IRRRPLFYAV SLLLPSIFLM VVDIVGFCLP PD SGERVSF KITLLLGYSV FLIIVSDTLP ATAIGTPLIG VYFVVCMALL VISLAETIFI VRLVHKQDLQ RPVPDWLRHL VLD RIAWIL CLGEQPMAHR PPATFQANKT DDCSGSDLLP AMGNHCSHVG GPQDLEKTPR GRGSPLPPPR EASLAVRGLL QELS SIRHF LEKRDEMREV ARDWLRVGYV LDRLLFRIYL LAVLAYSITL VTLWSI |
-Macromolecule #4: (3-ENDO)-8-METHYL-8-AZABICYCLO[3.2.1]OCT-3-YL 1H-INDOLE-3-CARBOXYLATE
Macromolecule | Name: (3-ENDO)-8-METHYL-8-AZABICYCLO[3.2.1]OCT-3-YL 1H-INDOLE-3-CARBOXYLATE type: ligand / ID: 4 / Number of copies: 5 / Formula: TKT |
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Molecular weight | Theoretical: 284.353 Da |
Chemical component information | ![]() ChemComp-TKT: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 80.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Applied symmetry - Point group: C5 (5 fold cyclic![]() |