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Yorodumi- EMDB-7882: Full-length 5-HT3A receptor in a serotonin-bound conformation- State 1 -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-7882 | ||||||||||||
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Title | Full-length 5-HT3A receptor in a serotonin-bound conformation- State 1 | ||||||||||||
Map data | serotonin bound 5HT3A receptor (state 1) | ||||||||||||
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 / acetylcholine-gated monoatomic cation-selective channel activity / inorganic cation transmembrane transport / cleavage furrow / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / presynaptic membrane ...Neurotransmitter receptors and postsynaptic signal transmission / serotonin-gated monoatomic cation channel activity / serotonin-activated cation-selective channel complex / serotonin receptor signaling pathway / serotonin binding / acetylcholine-gated monoatomic cation-selective channel activity / inorganic cation transmembrane transport / cleavage furrow / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / presynaptic membrane / postsynaptic membrane / neuron projection / axon / neuronal cell body / glutamatergic synapse / synapse / identical protein binding Similarity search - Function | ||||||||||||
Biological species | Mus musculus (house mouse) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.32 Å | ||||||||||||
Authors | Basak S / Chakrapani S | ||||||||||||
Funding support | United States, 3 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_7882.map.gz | 7.5 MB | EMDB map data format | |
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Header (meta data) | emd-7882-v30.xml emd-7882.xml | 19.1 KB 19.1 KB | Display Display | EMDB header |
Images | emd_7882.png | 137.9 KB | ||
Masks | emd_7882_msk_1.map | 103 MB | Mask map | |
Others | emd_7882_half_map_1.map.gz emd_7882_half_map_2.map.gz | 80.7 MB 80.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-7882 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7882 | HTTPS FTP |
-Related structure data
Related structure data | 6dg7MC 7883C 6dg8C C: citing same article (ref.) M: atomic model generated by this map |
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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_7882.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | serotonin bound 5HT3A receptor (state 1) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.064 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_7882_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: serotonin bound 5HT3A receptor (state 1), half map #1
File | emd_7882_half_map_1.map | ||||||||||||
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Annotation | serotonin bound 5HT3A receptor (state 1), half map #1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: serotonin bound 5HT3A receptor (state 1), half map #2
File | emd_7882_half_map_2.map | ||||||||||||
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Annotation | serotonin bound 5HT3A receptor (state 1), half map #2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Serotonin receptor
Entire | Name: Serotonin receptor5-HT receptor |
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Components |
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-Supramolecule #1: Serotonin receptor
Supramolecule | Name: Serotonin receptor / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 270 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) / Recombinant strain: sf9 |
-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: 52.52366 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
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 VTLWSIWHYS |
-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: |
-Macromolecule #5: water
Macromolecule | Name: water / type: ligand / ID: 5 / Number of copies: 5 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 3 mg/mL |
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Buffer | pH: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK I / Details: blot for 2.5 seconds. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal magnification: 130000 |
Sample stage | Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Frames/image: 2-39 / Number real images: 2810 / Average electron dose: 40.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Particle selection | Number selected: 749970 |
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CTF correction | Software - Name: Gctf (ver. 1.06) |
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
Initial angle assignment | Type: RANDOM ASSIGNMENT / Software - Name: RELION (ver. 2.1) |
Final 3D classification | Software - Name: RELION (ver. 2.1) |
Final angle assignment | Type: ANGULAR RECONSTITUTION / Software - Name: RELION (ver. 2.1) |
Final reconstruction | Applied symmetry - Point group: C5 (5 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.32 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 2.1) / Number images used: 103698 |
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: OTHER / Overall B value: 154 |
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Output model | PDB-6dg7: |