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- PDB-7mgw: 5-HT bound serotonin transporter reconstituted in lipid nanodisc ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7mgw | |||||||||
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Title | 5-HT bound serotonin transporter reconstituted in lipid nanodisc in NaCl in occluded conformation | |||||||||
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![]() | MEMBRANE PROTEIN / human serotonin transporter / transport / Fab / occluded | |||||||||
Function / homology | ![]() 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 / negative regulation of synaptic transmission, dopaminergic / sperm ejaculation / enteric nervous system development ...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 / negative regulation of synaptic transmission, dopaminergic / sperm ejaculation / enteric nervous system development / neurotransmitter transmembrane transporter activity / serotonin uptake / cellular response to cGMP / negative regulation of organ growth / sodium ion binding / monoamine transmembrane transporter activity / monoamine transport / conditioned place preference / serotonin binding / vasoconstriction / brain morphogenesis / neurotransmitter transport / antiporter activity / syntaxin-1 binding / amino acid transport / nitric-oxide synthase binding / membrane depolarization / social behavior / behavioral response to cocaine / negative regulation of neuron differentiation / sodium ion transmembrane transport / endomembrane system / monoatomic cation channel activity / positive regulation of cell cycle / cellular response to retinoic acid / response to nutrient / response to toxic substance / memory / platelet aggregation / circadian rhythm / actin filament binding / integrin binding / response to estradiol / presynaptic membrane / postsynaptic membrane / endosome membrane / response to hypoxia / response to xenobiotic stimulus / neuron projection / membrane raft / focal adhesion / synapse / positive regulation of gene expression / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
![]() | Yang, D. / Gouaux, E. | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 146.7 KB | Display | ![]() |
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PDB format | ![]() | 118.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1015.9 KB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 30 KB | Display | |
Data in CIF | ![]() | 42.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 23830MC ![]() 7li6C ![]() 7li7C ![]() 7li8C ![]() 7li9C ![]() 7liaC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Antibody , 2 types, 2 molecules BC
#2: Antibody | Mass: 12980.533 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#3: Antibody | Mass: 11776.065 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
-Protein / Sugars , 2 types, 2 molecules A
#1: Protein | Mass: 60677.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
-Non-polymers , 7 types, 16 molecules ![](data/chem/img/CL.gif)
![](data/chem/img/D12.gif)
![](data/chem/img/LNK.gif)
![](data/chem/img/HP6.gif)
![](data/chem/img/D10.gif)
![](data/chem/img/SRO.gif)
![](data/chem/img/CLR.gif)
![](data/chem/img/D12.gif)
![](data/chem/img/LNK.gif)
![](data/chem/img/HP6.gif)
![](data/chem/img/D10.gif)
![](data/chem/img/SRO.gif)
![](data/chem/img/CLR.gif)
#5: Chemical | ChemComp-CL / | ||||||||||
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#6: Chemical | ChemComp-D12 / #7: Chemical | ChemComp-LNK / | #8: Chemical | ChemComp-HP6 / #9: Chemical | ChemComp-D10 / | #10: Chemical | #11: Chemical | ChemComp-CLR / | |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: apo human serotonin transporter in complex with 15B8 Fab in NaCl Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES | ||||||||||||
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 55 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.17_3644: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 114222 / Symmetry type: POINT | ||||||||||||||||||||||||
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