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PXD013750

DataSet Summary

  • HostingRepository: PRIDE
  • AnnounceDate: 2019-05-15
  • AnnouncementXML: Submission_2019-05-15_02:49:38.xml
  • DigitalObjectIdentifier:
  • ReviewLevel: Peer-reviewed dataset
  • DatasetOrigin: Original data
  • RepositorySupport: Unsupported dataset by repository
  • PrimarySubmitter: Kasper Rand
  • Title: Conformational dynamics of the human serotonin transporter during substrate and drug binding
  • Description: The serotonin transporter (SERT), a member of the neurotransmitter:sodium symporter family, is responsible for termination of serotonergic signaling by re-uptake of serotonin (5-HT) into the presynaptic neuron. Its key role in synaptic transmission makes it a major drug target, e.g. for the treatment of depression, anxiety and post-traumatic stress. Here, we apply hydrogen-deuterium exchange mass spectrometry to probe the conformational dynamics of human SERT in the absence and presence of known substrates and targeted drugs. Our results reveal significant changes in dynamics in regions TM1, EL3, EL4, and TM12 upon binding co-transported ions (Na+/K+) and ligand-mediated changes in TM1, EL3 and EL4 upon binding 5-HT, the drugs S-citalopram, cocaine and ibogaine. Our results provide a comprehensive direct view of the conformational response of SERT upon binding both biologically relevant substrate/ions and ligands of pharmaceutical interest, thus advancing our understanding of the structure-function relationship in SERT.
  • SpeciesList: scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
  • ModificationList: No PTMs are included in the dataset
  • Instrument: Synapt MS

Dataset History

VersionDatetimeStatusChangeLog Entry
02019-05-07 04:03:02ID requested
12019-05-15 02:49:39announced

Publication List

  1. Möller IR, Slivacka M, Nielsen AK, Rasmussen SGF, Gether U, Loland CJ, Rand KD, Conformational dynamics of the human serotonin transporter during substrate and drug binding. Nat Commun, 10(1):1687(2019) [pubmed]

Keyword List

  1. ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)
  2. submitter keyword: HDX-MS
  3. Protein-ligand interactions
  4. Membrane proteins
  5. Mass Spectrometry

Contact List

    Kasper D. Rand
    • contact affiliation: Protein Analysis Group, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark
    • contact email: kasper.rand@sund.ku.dk
    • lab head:
    Kasper Rand
    • contact affiliation: Department of Pharmacy, University of Copenhagen
    • contact email: kasper.rand@sund.ku.dk
    • dataset submitter:

Full Dataset Link List

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  2. PRIDE project URI
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