PXD013841

PXD013841 is an original dataset announced via ProteomeXchange.

Title	Substrate-induced conformational dynamics of the dopamine transporter
Description	The dopamine transporter is a member of the neurotransmitter:sodium symporters (NSSs), which are responsible for termination of neurotransmission through Na+-driven reuptake of neurotransmitter from the extracellular space. Experimental evidence elucidating the coordinated conformational rearrangements related to the transport mechanism has so far been limited. Here we probe the global Na+- and dopamine-induced conformational dynamics of the wild-type Drosophila melanogaster dopamine transporter using hydrogen-deuterium exchange mass spectrometry. We identify Na+- and dopamine-induced changes in specific regions of the transporter, suggesting their involvement in protein conformational transitions. Furthermore, we detect ligand-dependent slow cooperative fluctuations of helical stretches in several domains of the transporter, which could be a molecular mechanism that assists in the transporter function. Our results provide a framework for understanding the molecular mechanism underlying the function of NSSs by revealing detailed insight into the state-dependent conformational changes associated with the alternating access model of the dopamine transporter.
HostingRepository	PRIDE
AnnounceDate	2019-11-12
AnnouncementXML	Submission_2019-11-11_17:59:31.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kasper Rand
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-14 05:42:40	ID requested
⏵ 1	2019-11-11 17:59:32	announced

Nielsen AK, M, ö, ller IR, Wang Y, Rasmussen SGF, Lindorff-Larsen K, Rand KD, Loland CJ, Substrate-induced conformational dynamics of the dopamine transporter. Nat Commun, 10(1):2714(2019) [pubmed]

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

submitter keyword: 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/2019/11/PXD013841

PRIDE project URI

• PRIDE
  1. PXD013841
     1. Label: PRIDE project
     2. Name: Substrate-induced conformational dynamics of the dopamine transporter