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Yorodumi- EMDB-23830: 5-HT bound serotonin transporter reconstituted in lipid nanodisc ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23830 | |||||||||
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Title | 5-HT bound serotonin transporter reconstituted in lipid nanodisc in NaCl in occluded conformation | |||||||||
Map data | sharpen man | |||||||||
Sample |
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Function / homology | Function and homology information negative regulation of cerebellar granule cell precursor proliferation / regulation of thalamus size / Serotonin clearance from the synaptic cleft / serotonergic synapse / positive regulation of serotonin secretion / cocaine binding / serotonin:sodium:chloride symporter activity / sperm ejaculation / neurotransmitter transmembrane transporter activity / negative regulation of synaptic transmission, dopaminergic ...negative regulation of cerebellar granule cell precursor proliferation / regulation of thalamus size / Serotonin clearance from the synaptic cleft / serotonergic synapse / positive regulation of serotonin secretion / cocaine binding / serotonin:sodium:chloride symporter activity / sperm ejaculation / neurotransmitter transmembrane transporter activity / negative regulation of synaptic transmission, dopaminergic / monoamine transmembrane transporter activity / serotonin uptake / monoamine transport / enteric nervous system development / negative regulation of organ growth / cellular response to cGMP / sodium ion binding / serotonin binding / neurotransmitter transport / vasoconstriction / brain morphogenesis / antiporter activity / syntaxin-1 binding / nitric-oxide synthase binding / social behavior / membrane depolarization / negative regulation of neuron differentiation / sodium ion transmembrane transport / endomembrane system / positive regulation of cell cycle / monoatomic cation channel activity / cellular response to retinoic acid / response to nutrient / memory / response to toxic substance / platelet aggregation / circadian rhythm / actin filament binding / integrin binding / response to estradiol / presynaptic membrane / postsynaptic membrane / response to hypoxia / endosome membrane / neuron projection / response to xenobiotic stimulus / membrane raft / focal adhesion / synapse / positive regulation of gene expression / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Yang D / Gouaux E | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Sci Adv / Year: 2021 Title: Illumination of serotonin transporter mechanism and role of the allosteric site. Authors: Dongxue Yang / Eric Gouaux / Abstract: The serotonin transporter (SERT) terminates serotonin signaling by using sodium and chloride gradients to drive reuptake of serotonin into presynaptic neurons and is the target of widely used ...The serotonin transporter (SERT) terminates serotonin signaling by using sodium and chloride gradients to drive reuptake of serotonin into presynaptic neurons and is the target of widely used medications to treat neuropsychiatric disorders. Despite decades of study, the molecular mechanism of serotonin transport, the coupling to ion gradients, and the role of the allosteric site have remained elusive. Here, we present cryo–electron microscopy structures of SERT in serotonin-bound and serotonin-free states, in the presence of sodium or potassium, resolving all fundamental states of the transport cycle. From the SERT-serotonin complex, we localize the substrate-bound allosteric site, formed by an aromatic pocket positioned in the scaffold domain in the extracellular vestibule, connected to the central site via a short tunnel. Together with elucidation of multiple apo state conformations, we provide previously unseen structural understanding of allosteric modulation, demonstrating how SERT binds serotonin from synaptic volumes and promotes unbinding into the presynaptic neurons. | |||||||||
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_23830.map.gz | 230 MB | EMDB map data format | |
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Header (meta data) | emd-23830-v30.xml emd-23830.xml | 16 KB 16 KB | Display Display | EMDB header |
Images | emd_23830.png | 105.6 KB | ||
Others | emd_23830_additional_1.map.gz | 120 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23830 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23830 | HTTPS FTP |
-Related structure data
Related structure data | 7mgwMC 7li6C 7li7C 7li8C 7li9C 7liaC 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_23830.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | sharpen man | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.648 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: unsharpen map
File | emd_23830_additional_1.map | ||||||||||||
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Annotation | unsharpen map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : apo human serotonin transporter in complex with 15B8 Fab in NaCl
+Supramolecule #1: apo human serotonin transporter in complex with 15B8 Fab in NaCl
+Macromolecule #1: Sodium-dependent serotonin transporter
+Macromolecule #2: variable domain of 15B8 antibody Fab heavy chain
+Macromolecule #3: variable domain of 15B8 antiboty Fab light chain
+Macromolecule #5: CHLORIDE ION
+Macromolecule #6: DODECANE
+Macromolecule #7: PENTANE
+Macromolecule #8: HEPTANE
+Macromolecule #9: DECANE
+Macromolecule #10: SEROTONIN
+Macromolecule #11: CHOLESTEROL
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 55.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER / Details: ab initio |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 114222 |