+Open data
-Basic information
Entry | Database: PDB / ID: 7li6 | |||||||||
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Title | apo SERT reconstituted in lipid nanodisc in KCl | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / serotonin / human serotonin transporter / transport | |||||||||
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 / sperm ejaculation / serotonin:sodium:chloride symporter activity / 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 / sperm ejaculation / serotonin:sodium:chloride symporter activity / neurotransmitter transmembrane transporter activity / negative regulation of synaptic transmission, dopaminergic / serotonin uptake / enteric nervous system development / monoamine transmembrane transporter activity / cellular response to cGMP / monoamine transport / negative regulation of organ growth / sodium ion binding / serotonin binding / vasoconstriction / neurotransmitter transport / brain morphogenesis / antiporter activity / syntaxin-1 binding / nitric-oxide synthase binding / membrane depolarization / social behavior / sodium ion transmembrane transport / negative regulation of neuron differentiation / endomembrane system / positive regulation of cell cycle / cellular response to retinoic acid / monoatomic cation channel activity / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Yang, D. / Gouaux, E. | |||||||||
Funding support | United States, 2items
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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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7li6.cif.gz | 147.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7li6.ent.gz | 118.7 KB | Display | PDB format |
PDBx/mmJSON format | 7li6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/li/7li6 ftp://data.pdbj.org/pub/pdb/validation_reports/li/7li6 | HTTPS FTP |
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-Related structure data
Related structure data | 23361MC 7li7C 7li8C 7li9C 7liaC 7mgwC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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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 natural source / Source: (natural) Mus musculus (house mouse) |
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#3: Antibody | Mass: 11776.065 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) |
-Protein / Sugars , 2 types, 2 molecules A
#1: Protein | Mass: 60875.957 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SLC6A4, HTT, SERT / Production host: Homo sapiens (human) / References: UniProt: P31645 |
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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 , 6 types, 24 molecules
#5: Chemical | ChemComp-CL / | ||||||
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#6: Chemical | ChemComp-R16 / | ||||||
#7: Chemical | ChemComp-HP6 / #8: Chemical | ChemComp-D10 / #9: Chemical | #10: Chemical | ChemComp-LNK / |
-Details
Has ligand of interest | N |
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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 |
-Sample preparation
Component | Name: apo state of human serotonin transporter in complex with 15B8 Fab in KCl Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES | ||||||||||||
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Source (natural) |
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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 |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 52 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-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: 707210 / Symmetry type: POINT | ||||||||||||||||||||||||
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