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- EMDB-23363: apo serotonin transporter reconstituted in lipid nanodisc in pres... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-23363 | |||||||||
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Title | apo serotonin transporter reconstituted in lipid nanodisc in presence of NaCl in inward open conformation | |||||||||
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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 / serotonin uptake / cellular response to cGMP / negative regulation of organ growth / sodium ion binding / neurotransmitter transmembrane transporter activity / conditioned place preference / monoamine transmembrane transporter activity / monoamine transport / serotonin binding / vasoconstriction / brain morphogenesis / neurotransmitter transport / antiporter activity / syntaxin-1 binding / amino acid transport / nitric-oxide synthase binding / membrane depolarization / behavioral response to cocaine / social behavior / 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 / 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 | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 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 | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 229.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.9 KB 14.9 KB | Display Display | ![]() |
Images | ![]() | 101.1 KB | ||
Others | ![]() | 119.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7li8MC ![]() 7li6C ![]() 7li7C ![]() 7li9C ![]() 7liaC ![]() 7mgwC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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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Annotation | sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: unsharpened map
File | emd_23363_additional_1.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : apo human serotonin transporter in complex with 15B8 Fab in NaCl
Entire | Name: apo human serotonin transporter in complex with 15B8 Fab in NaCl |
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Components |
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-Supramolecule #1: apo human serotonin transporter in complex with 15B8 Fab in NaCl
Supramolecule | Name: apo human serotonin transporter in complex with 15B8 Fab in NaCl type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Sodium-dependent serotonin transporter
Macromolecule | Name: Sodium-dependent serotonin transporter / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 60.875957 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: RETWGKKVDF LLSVIGYAVD LGNVWRFPYI CYQNGGGAFL LPYTIMAIFG GIPLFYMELA LGQYHRNGCI SIWRKICPIF KGIGYAICI IAFYIASYYN TIMAWALYYL ISSFTDQLPW TSCKNSWNTG NCTNYFSEDN ITWTLHSTSP AEEFYTRHVL Q IHRSKGLQ ...String: RETWGKKVDF LLSVIGYAVD LGNVWRFPYI CYQNGGGAFL LPYTIMAIFG GIPLFYMELA LGQYHRNGCI SIWRKICPIF KGIGYAICI IAFYIASYYN TIMAWALYYL ISSFTDQLPW TSCKNSWNTG NCTNYFSEDN ITWTLHSTSP AEEFYTRHVL Q IHRSKGLQ DLGGISWQLA LCIMLIFTVI YFSIWKGVKT SGKVVWVTAT FPYIILSVLL VRGATLPGAW RGVLFYLKPN WQ KLLETGV WIDAAAQIFF SLGPGFGVLL AFASYNKFNN NCYQDALVTS VVNCMTSFVS GFVIFTVLGY MAEMRNEDVS EVA KDAGPS LLFITYAEAI ANMPASTFFA IIFFLMLITL GLDSTFAGLE GVITAVLDEF PHVWAKRRER FVLAVVITCF FGSL VTLTF GGAYVVKLLE EYATGPAVLT VALIEAVAVS WFYGITQFCR DVKEMLGFSP GWFWRICWVA ISPLFLLFII CSFLM SPPQ LRLFQYNYPY WSIILGYCIG TSSFICIPTY IAYRLIITPG TFKERIIKSI TPETP |
-Macromolecule #2: variable domain of 15B8 antibody Fab heavy chain
Macromolecule | Name: variable domain of 15B8 antibody Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 12.980533 KDa |
Sequence | String: QVQLQQSGPE LVKLGASVRI SCKASGYRFS YSWMNWVKQR PGKGLEWIGR IYPGDGDTKY SGKFKGKATL TADKSSSTVY MQLSSLTSE DSAVYFCARS AYGSEGFAMD YWGQGTSVT |
-Macromolecule #3: variable domain of 15B8 antibody Fab light chain
Macromolecule | Name: variable domain of 15B8 antibody Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 11.776065 KDa |
Sequence | String: DIVLTQSPAS LAVSLGQRAT ISCRASESVD NYGISFLNWF QQKPGQPPKL LIYAASNQGS GVPARFSGSG SGTYFSLNIH PMEEDDTAV YFCQQTKGVS WTFGGGTKVE I |
-Macromolecule #5: HEXADECANE
Macromolecule | Name: HEXADECANE / type: ligand / ID: 5 / Number of copies: 1 / Formula: R16 |
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Molecular weight | Theoretical: 226.441 Da |
Chemical component information | ![]() ChemComp-R16: |
-Macromolecule #6: DECANE
Macromolecule | Name: DECANE / type: ligand / ID: 6 / Number of copies: 1 / Formula: D10 |
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Molecular weight | Theoretical: 142.282 Da |
Chemical component information | ![]() ChemComp-D10: |
-Macromolecule #7: DODECANE
Macromolecule | Name: DODECANE / type: ligand / ID: 7 / Number of copies: 3 / Formula: D12 |
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Molecular weight | Theoretical: 170.335 Da |
Chemical component information | ![]() ChemComp-D12: |
-Macromolecule #8: HEPTANE
Macromolecule | Name: HEPTANE / type: ligand / ID: 8 / Number of copies: 6 / Formula: HP6 |
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Molecular weight | Theoretical: 100.202 Da |
Chemical component information | ![]() ChemComp-HP6: |
-Macromolecule #9: PENTANE
Macromolecule | Name: PENTANE / type: ligand / ID: 9 / Number of copies: 1 / Formula: LNK |
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Molecular weight | Theoretical: 72.149 Da |
Chemical component information | ![]() ChemComp-LNK: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER / Details: Ab initio |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 343085 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |