PXD013750

PXD013750 is an original dataset announced via ProteomeXchange.

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.
HostingRepository	PRIDE
AnnounceDate	2019-05-15
AnnouncementXML	Submission_2019-05-15_02:49:38.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kasper Rand
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-07 04:03:02	ID requested
⏵ 1	2019-05-15 02:49:39	announced

M, ö, ller 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]

ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)

submitter keyword: HDX-MS

Protein-ligand interactions

Membrane proteins

Mass Spectrometry

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013750

PRIDE project URI

• PRIDE
  1. PXD013750
     1. Label: PRIDE project
     2. Name: Conformational dynamics of the human serotonin transporter during substrate and drug binding