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Substrate-induced conformational dynamics of the dopamine transporter
by
Möller, Ingvar R.
, Lindorff-Larsen, Kresten
, Nielsen, Anne Kathrine
, Rasmussen, Søren G. F.
, Loland, Claus J.
, Rand, Kasper D.
, Wang, Yong
in
101/58
/ 631/1647/296
/ 631/378/2587
/ 631/535
/ 631/57
/ 82/80
/ 82/83
/ Deuterium
/ Domains
/ Dopamine
/ Dopamine - metabolism
/ Dopamine Plasma Membrane Transport Proteins - chemistry
/ Dopamine Plasma Membrane Transport Proteins - isolation & purification
/ Dopamine Plasma Membrane Transport Proteins - metabolism
/ Dopamine transporter
/ Drosophila Proteins - chemistry
/ Drosophila Proteins - isolation & purification
/ Drosophila Proteins - metabolism
/ Fruit flies
/ HEK293 Cells
/ Humanities and Social Sciences
/ Humans
/ Hydrogen-deuterium exchange
/ Ligands
/ Mass Spectrometry
/ Mass spectroscopy
/ Molecular Dynamics Simulation
/ multidisciplinary
/ Neurotransmission
/ Neurotransmitters
/ Protein Conformation, alpha-Helical - physiology
/ Protein Domains - physiology
/ Recombinant Proteins - chemistry
/ Recombinant Proteins - isolation & purification
/ Recombinant Proteins - metabolism
/ Science
/ Science (multidisciplinary)
/ Sodium
/ Sodium - metabolism
/ Substrates
/ Variation
2019
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Substrate-induced conformational dynamics of the dopamine transporter
by
Möller, Ingvar R.
, Lindorff-Larsen, Kresten
, Nielsen, Anne Kathrine
, Rasmussen, Søren G. F.
, Loland, Claus J.
, Rand, Kasper D.
, Wang, Yong
in
101/58
/ 631/1647/296
/ 631/378/2587
/ 631/535
/ 631/57
/ 82/80
/ 82/83
/ Deuterium
/ Domains
/ Dopamine
/ Dopamine - metabolism
/ Dopamine Plasma Membrane Transport Proteins - chemistry
/ Dopamine Plasma Membrane Transport Proteins - isolation & purification
/ Dopamine Plasma Membrane Transport Proteins - metabolism
/ Dopamine transporter
/ Drosophila Proteins - chemistry
/ Drosophila Proteins - isolation & purification
/ Drosophila Proteins - metabolism
/ Fruit flies
/ HEK293 Cells
/ Humanities and Social Sciences
/ Humans
/ Hydrogen-deuterium exchange
/ Ligands
/ Mass Spectrometry
/ Mass spectroscopy
/ Molecular Dynamics Simulation
/ multidisciplinary
/ Neurotransmission
/ Neurotransmitters
/ Protein Conformation, alpha-Helical - physiology
/ Protein Domains - physiology
/ Recombinant Proteins - chemistry
/ Recombinant Proteins - isolation & purification
/ Recombinant Proteins - metabolism
/ Science
/ Science (multidisciplinary)
/ Sodium
/ Sodium - metabolism
/ Substrates
/ Variation
2019
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Substrate-induced conformational dynamics of the dopamine transporter
by
Möller, Ingvar R.
, Lindorff-Larsen, Kresten
, Nielsen, Anne Kathrine
, Rasmussen, Søren G. F.
, Loland, Claus J.
, Rand, Kasper D.
, Wang, Yong
in
101/58
/ 631/1647/296
/ 631/378/2587
/ 631/535
/ 631/57
/ 82/80
/ 82/83
/ Deuterium
/ Domains
/ Dopamine
/ Dopamine - metabolism
/ Dopamine Plasma Membrane Transport Proteins - chemistry
/ Dopamine Plasma Membrane Transport Proteins - isolation & purification
/ Dopamine Plasma Membrane Transport Proteins - metabolism
/ Dopamine transporter
/ Drosophila Proteins - chemistry
/ Drosophila Proteins - isolation & purification
/ Drosophila Proteins - metabolism
/ Fruit flies
/ HEK293 Cells
/ Humanities and Social Sciences
/ Humans
/ Hydrogen-deuterium exchange
/ Ligands
/ Mass Spectrometry
/ Mass spectroscopy
/ Molecular Dynamics Simulation
/ multidisciplinary
/ Neurotransmission
/ Neurotransmitters
/ Protein Conformation, alpha-Helical - physiology
/ Protein Domains - physiology
/ Recombinant Proteins - chemistry
/ Recombinant Proteins - isolation & purification
/ Recombinant Proteins - metabolism
/ Science
/ Science (multidisciplinary)
/ Sodium
/ Sodium - metabolism
/ Substrates
/ Variation
2019
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Substrate-induced conformational dynamics of the dopamine transporter
Journal Article
Substrate-induced conformational dynamics of the dopamine transporter
2019
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Overview
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.
The dopamine transporter is responsible for termination of neurotransmission through Na
+
-driven reuptake of neurotransmitter from the extracellular space. Here authors use hydrogen-deuterium exchange mass spectrometry to monitor Na
+
- and dopamine-induced conformational dynamics of the dopamine transporter.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/535
/ 631/57
/ 82/80
/ 82/83
/ Domains
/ Dopamine
/ Dopamine Plasma Membrane Transport Proteins - chemistry
/ Dopamine Plasma Membrane Transport Proteins - isolation & purification
/ Dopamine Plasma Membrane Transport Proteins - metabolism
/ Drosophila Proteins - chemistry
/ Drosophila Proteins - isolation & purification
/ Drosophila Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Ligands
/ Molecular Dynamics Simulation
/ Protein Conformation, alpha-Helical - physiology
/ Protein Domains - physiology
/ Recombinant Proteins - chemistry
/ Recombinant Proteins - isolation & purification
/ Recombinant Proteins - metabolism
/ Science
/ Sodium
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