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- EMDB-29418: Full-length mouse 5-HT3A receptor in complex with serotonin, open-like -
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Open data
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Basic information
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Title | Full-length mouse 5-HT3A receptor in complex with serotonin, open-like | |||||||||
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![]() | agonist / cys-loop / pLGIC / ion channel / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() 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 | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.75 Å | |||||||||
![]() | Felt KC / Chakrapani S | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for partial agonism in 5-HT receptors. Authors: Kevin Felt / Madeleine Stauffer / Leslie Salas-Estrada / Peter R Guzzo / Dejian Xie / Jinkun Huang / Marta Filizola / Sudha Chakrapani / ![]() ![]() Abstract: Hyperactivity of serotonin 3 receptors (5-HTR) underlies pathologies associated with irritable bowel syndrome and chemotherapy-induced nausea and vomiting. Setrons, a class of high-affinity ...Hyperactivity of serotonin 3 receptors (5-HTR) underlies pathologies associated with irritable bowel syndrome and chemotherapy-induced nausea and vomiting. Setrons, a class of high-affinity competitive antagonists, are used in the treatment of these conditions. Although generally effective for chemotherapy-induced nausea and vomiting, the use of setrons for treating irritable bowel syndrome has been impaired by adverse side effects. Partial agonists are now being considered as an alternative strategy, with potentially less severe side effects than full antagonists. However, a structural understanding of how these ligands work is lacking. Here, we present high-resolution cryogenic electron microscopy structures of the mouse 5-HTR in complex with partial agonists (SMP-100 and ALB-148471) captured in pre-activated and open-like conformational states. Molecular dynamics simulations were used to assess the stability of drug-binding poses and interactions with the receptor over time. Together, these studies reveal mechanisms for the functional differences between orthosteric partial agonists, full agonists and antagonists of the 5-HTR. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 7.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.9 KB 17.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.6 KB | Display | ![]() |
Images | ![]() | 45.5 KB | ||
Filedesc metadata | ![]() | 6.2 KB | ||
Others | ![]() ![]() | 81.1 MB 80.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8fsbMC ![]() 8frwC ![]() 8frxC ![]() 8frzC ![]() 8fspC ![]() 8fszC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_29418_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_29418_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : 5-HT3A pentamer in complex with orthosteric ligand serotonin
Entire | Name: 5-HT3A pentamer in complex with orthosteric ligand serotonin |
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Components |
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-Supramolecule #1: 5-HT3A pentamer in complex with orthosteric ligand serotonin
Supramolecule | Name: 5-HT3A pentamer in complex with orthosteric ligand serotonin type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 331 KDa |
-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: 62.349812 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: WSHPQFEKGG GSGGGSGGGS WSHPQFEKGG GSGGGSGGGS WSHPQFEKGG GSGGGSGGGS WSHPQFEKEN LYFQGATQAR DTTQPALLR LSDHLLANYK KGVRPVRDWR KPTTVSIDVI MYAILNVDEK NQVLTTYIWY RQYWTDEFLQ WTPEDFDNVT K LSIPTDSI ...String: WSHPQFEKGG GSGGGSGGGS WSHPQFEKGG GSGGGSGGGS WSHPQFEKGG GSGGGSGGGS WSHPQFEKEN LYFQGATQAR DTTQPALLR LSDHLLANYK KGVRPVRDWR KPTTVSIDVI MYAILNVDEK NQVLTTYIWY RQYWTDEFLQ WTPEDFDNVT K LSIPTDSI WVPDILINEF VDVGKSPNIP YVYVHHRGEV QNYKPLQLVT ACSLDIYNFP FDVQNCSLTF TSWLHTIQDI NI TLWRSPE EVRSDKSIFI NQGEWELLEV FPQFKEFSID ISNSYAEMKF YVIIRRRPLF YAVSLLLPSI FLMVVDIVGF CLP PDSGER VSFKITLLLG YSVFLIIVSD TLPATAIGTP LIGVYFVVCM ALLVISLAET IFIVRLVHKQ DLQRPVPDWL RHLV LDRIA WILCLGEQPM AHRPPATFQA NKTDDCSGSD LLPAMGNHCS HVGGPQDLEK TPRGRGSPLP PPREASLAVR GLLQE LSSI RHFLEKRDEM REVARDWLRV GYVLDRLLFR IYLLAVLAYS ITLVTLWSIW HYSENLYFQG TETSQVAPA UniProtKB: 5-hydroxytryptamine receptor 3A |
-Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 15 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #3: SEROTONIN
Macromolecule | Name: SEROTONIN / type: ligand / ID: 3 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 2.6 mg/mL |
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Buffer | pH: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK I |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | ![]() PDB-8fsb: |