Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

Title: Mechanism of the association between Na+ binding and conformations at the intracellular gate in neurotransmitter:sodium symporters

Abstract

Neurotransmitter:sodium symporters (NSSs) terminate neurotransmission by Na+-dependent reuptake of released neurotransmitters. Previous studies suggested that Na+-binding reconfigures dynamically coupled structural elements in an allosteric interaction network (AIN) responsible for function-related conformational changes, but the intramolecular pathway of this mechanism has remained uncharted. Here we describe a new approach for the modeling and analysis of intramolecular dynamics in the bacterial NSS homolog LeuT. From microsecond-scale molecular dynamics simulations and cognate experimental verifications in both LeuT and human dopamine transporter (hDAT), we apply the novel method to identify the composition and the dynamic properties of their conserved AIN. In LeuT, two different perturbations disrupting Na+ binding and transport (i.e. replacing Na+ with Li+ or the Y268A mutation at the intracellular gate) affect the AIN in strikingly similar ways. In contrast, other mutations that affect the intracellular gate (i.e. R5A and D369A) do not significantly impair Na+ cooperativity and transport. Our analysis shows these perturbations to have much lesser effects on the AIN, underscoring the sensitivity of this novel method to the mechanistic nature of the perturbation. Notably, this set of observations holds as well for hDAT, where the aligned Y335A, R60A, and D436A mutations also produce different impacts on Na+ dependence. Furthermore,more » the detailed AIN generated from our method is shown to connect Na+ binding with global conformational changes that are critical for the transport mechanism. Lastly, that the AIN between the Na+ binding sites and the intracellular gate in bacterial LeuT resembles that in eukaryotic hDAT highlights the conservation of allosteric pathways underlying NSS function.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [4];  [4];  [2];  [3];  [5];  [6]
+ Show Author Affiliations
  1. Weill Medical College of Cornell Univ., New York, NY (United States); Cornell Univ., Ithaca, NY (United States)
  2. Columbia Univ. College of Physicians and Surgeons, New York, NY (United States); New York State Psychiatric Institute, New York, NY (United States)
  3. Univ. of Calgary, Calgary, AB (Canada)
  4. Univ. of Copenhagen, Copenhagen (Denmark)
  5. Weill Medical College of Cornell Univ., New York, NY (United States)
  6. Weill Medical College of Cornell Univ., New York, NY (United States); National Institutes of Health, Baltimore, MD (United States)
Publication Date:
Research Org.:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF); UT-Battelle LLC/ORNL, Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1348222
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Biological Chemistry
Additional Journal Information:
Journal Volume: 290; Journal Issue: 22; Journal ID: ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular Biology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; molecular dynamics; neurotransmitter transport; potential of mean force calculation; allosteric regulation; dopamine transporter; metal ion-protein interaction

Citation Formats

Stolzenberg, Sebastian, Quick, Matthias, Zhao, Chunfeng, Gotfryd, Kamil, Khelashvili, George, Gether, Ulrik, Loland, Claus J., Javitch, Jonathan A., Noskov, Sergei, Weinstein, Harel, and Shi, Lei. Mechanism of the association between Na+ binding and conformations at the intracellular gate in neurotransmitter:sodium symporters. United States: N. p., 2015. Web. doi:10.1074/jbc.m114.625343.
Copy to clipboard
Stolzenberg, Sebastian, Quick, Matthias, Zhao, Chunfeng, Gotfryd, Kamil, Khelashvili, George, Gether, Ulrik, Loland, Claus J., Javitch, Jonathan A., Noskov, Sergei, Weinstein, Harel, & Shi, Lei. Mechanism of the association between Na+ binding and conformations at the intracellular gate in neurotransmitter:sodium symporters. United States. https://doi.org/10.1074/jbc.m114.625343
Copy to clipboard
Stolzenberg, Sebastian, Quick, Matthias, Zhao, Chunfeng, Gotfryd, Kamil, Khelashvili, George, Gether, Ulrik, Loland, Claus J., Javitch, Jonathan A., Noskov, Sergei, Weinstein, Harel, and Shi, Lei. Mon . "Mechanism of the association between Na+ binding and conformations at the intracellular gate in neurotransmitter:sodium symporters". United States. https://doi.org/10.1074/jbc.m114.625343. https://www.osti.gov/servlets/purl/1348222.
Copy to clipboard
@article{osti_1348222,
title = {Mechanism of the association between Na+ binding and conformations at the intracellular gate in neurotransmitter:sodium symporters},
author = {Stolzenberg, Sebastian and Quick, Matthias and Zhao, Chunfeng and Gotfryd, Kamil and Khelashvili, George and Gether, Ulrik and Loland, Claus J. and Javitch, Jonathan A. and Noskov, Sergei and Weinstein, Harel and Shi, Lei},
abstractNote = {Neurotransmitter:sodium symporters (NSSs) terminate neurotransmission by Na+-dependent reuptake of released neurotransmitters. Previous studies suggested that Na+-binding reconfigures dynamically coupled structural elements in an allosteric interaction network (AIN) responsible for function-related conformational changes, but the intramolecular pathway of this mechanism has remained uncharted. Here we describe a new approach for the modeling and analysis of intramolecular dynamics in the bacterial NSS homolog LeuT. From microsecond-scale molecular dynamics simulations and cognate experimental verifications in both LeuT and human dopamine transporter (hDAT), we apply the novel method to identify the composition and the dynamic properties of their conserved AIN. In LeuT, two different perturbations disrupting Na+ binding and transport (i.e. replacing Na+ with Li+ or the Y268A mutation at the intracellular gate) affect the AIN in strikingly similar ways. In contrast, other mutations that affect the intracellular gate (i.e. R5A and D369A) do not significantly impair Na+ cooperativity and transport. Our analysis shows these perturbations to have much lesser effects on the AIN, underscoring the sensitivity of this novel method to the mechanistic nature of the perturbation. Notably, this set of observations holds as well for hDAT, where the aligned Y335A, R60A, and D436A mutations also produce different impacts on Na+ dependence. Furthermore, the detailed AIN generated from our method is shown to connect Na+ binding with global conformational changes that are critical for the transport mechanism. Lastly, that the AIN between the Na+ binding sites and the intracellular gate in bacterial LeuT resembles that in eukaryotic hDAT highlights the conservation of allosteric pathways underlying NSS function.},
doi = {10.1074/jbc.m114.625343},
journal = {Journal of Biological Chemistry},
number = 22,
volume = 290,
place = {United States},
year = {Mon Apr 13 00:00:00 EDT 2015},
month = {Mon Apr 13 00:00:00 EDT 2015}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1074/jbc.m114.625343
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal
Citation Metrics:
Cited by: 41 works
Citation information provided by
Web of Science
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referenced in this record:

Unlocking the molecular secrets of sodium-coupled transporters
journal, May 2009

  • Krishnamurthy, Harini; Piscitelli, Chayne L.; Gouaux, Eric
  • Nature, Vol. 459, Issue 7245
  • DOI: 10.1038/nature08143

Mechanism for alternating access in neurotransmitter transporters
journal, July 2008

  • Forrest, L. R.; Zhang, Y. -W.; Jacobs, M. T.
  • Proceedings of the National Academy of Sciences, Vol. 105, Issue 30
  • DOI: 10.1073/pnas.0804659105

Substrate Binding and Formation of an Occluded State in the Leucine Transporter
journal, March 2008

Coupled Global and Local Changes Direct Substrate Translocation by Neurotransmitter-Sodium Symporter Ortholog LeuT
journal, August 2013

Two mechanisms of ion selectivity in protein binding sites
journal, November 2010

  • Yu, H.; Noskov, S. Y.; Roux, B.
  • Proceedings of the National Academy of Sciences, Vol. 107, Issue 47
  • DOI: 10.1073/pnas.1007150107

X-ray structure of dopamine transporter elucidates antidepressant mechanism
journal, September 2013

  • Penmatsa, Aravind; Wang, Kevin H.; Gouaux, Eric
  • Nature, Vol. 503, Issue 7474
  • DOI: 10.1038/nature12533

The Role of Local Hydration and Hydrogen-Bonding Dynamics in Ion and Solute Release from Ion-Coupled Secondary Transporters
journal, March 2011

  • Zhao, Chunfeng; Noskov, Sergei Yu.
  • Biochemistry, Vol. 50, Issue 11
  • DOI: 10.1021/bi101454f

Ion/substrate-dependent conformational dynamics of a bacterial homolog of neurotransmitter:sodium symporters
journal, June 2010

  • Claxton, Derek P.; Quick, Matthias; Shi, Lei
  • Nature Structural & Molecular Biology, Vol. 17, Issue 7
  • DOI: 10.1038/nsmb.1854

Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters
journal, July 2005

  • Yamashita, Atsuko; Singh, Satinder K.; Kawate, Toshimitsu
  • Nature, Vol. 437, Issue 7056
  • DOI: 10.1038/nature03978

A Competitive Inhibitor Traps LeuT in an Open-to-Out Conformation
journal, December 2008

Ion-Controlled Conformational Dynamics in the Outward-Open Transition from an Occluded State of LeuT
journal, September 2012

Substrate-modulated gating dynamics in a Na+-coupled neurotransmitter transporter homologue
journal, April 2011

  • Zhao, Yongfang; Terry, Daniel S.; Shi, Lei
  • Nature, Vol. 474, Issue 7349
  • DOI: 10.1038/nature09971

Single-molecule dynamics of gating in a neurotransmitter transporter homologue
journal, May 2010

  • Zhao, Yongfang; Terry, Daniel; Shi, Lei
  • Nature, Vol. 465, Issue 7295
  • DOI: 10.1038/nature09057

Scalable molecular dynamics with NAMD
journal, January 2005

  • Phillips, James C.; Braun, Rosemary; Wang, Wei
  • Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802
  • DOI: 10.1002/jcc.20289

Improved Treatment of the Protein Backbone in Empirical Force Fields
journal, January 2004

  • MacKerell, Alexander D.; Feig, Michael; Brooks, Charles L.
  • Journal of the American Chemical Society, Vol. 126, Issue 3
  • DOI: 10.1021/ja036959e

Constant pressure molecular dynamics simulation: The Langevin piston method
journal, September 1995

  • Feller, Scott E.; Zhang, Yuhong; Pastor, Richard W.
  • The Journal of Chemical Physics, Vol. 103, Issue 11
  • DOI: 10.1063/1.470648

VMD: Visual molecular dynamics
journal, February 1996

Molecular signatures of G-protein-coupled receptors
journal, February 2013

  • Venkatakrishnan, A. J.; Deupi, Xavier; Lebon, Guillaume
  • Nature, Vol. 494, Issue 7436
  • DOI: 10.1038/nature11896

Satisfying Hydrogen Bonding Potential in Proteins
journal, May 1994

  • McDonald, Ian K.; Thornton, Janet M.
  • Journal of Molecular Biology, Vol. 238, Issue 5
  • DOI: 10.1006/jmbi.1994.1334

CHARMM: The biomolecular simulation program
journal, July 2009

  • Brooks, B. R.; Brooks, C. L.; Mackerell, A. D.
  • Journal of Computational Chemistry, Vol. 30, Issue 10
  • DOI: 10.1002/jcc.21287

Regulation of the dopamine transporter: Aspects relevant to psychostimulant drugs of abuse
journal, January 2010

Monitoring the function of membrane transport proteins in detergent-solubilized form
journal, February 2007

  • Quick, M.; Javitch, J. A.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 9
  • DOI: 10.1073/pnas.0609573104

Experimental conditions can obscure the second high-affinity site in LeuT
journal, January 2012

  • Quick, Matthias; Shi, Lei; Zehnpfennig, Britta
  • Nature Structural & Molecular Biology, Vol. 19, Issue 2
  • DOI: 10.1038/nsmb.2197

A rapid, sensitive, and specific method for the determination of protein in dilute solution
journal, December 1973

X-ray structures of LeuT in substrate-free outward-open and apo inward-open states
journal, January 2012

Chloride binding site of neurotransmitter sodium symporters
journal, May 2013

  • Kantcheva, A. K.; Quick, M.; Shi, L.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 21
  • DOI: 10.1073/pnas.1221279110

Generation of an activating Zn2+ switch in the dopamine transporter: Mutation of an intracellular tyrosine constitutively alters the conformational equilibrium of the transport cycle
journal, January 2002

  • Loland, C. J.; Norregaard, L.; Litman, T.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 3
  • DOI: 10.1073/pnas.032386299

Control of Ion Selectivity in LeuT: Two Na+ Binding Sites with Two Different Mechanisms
journal, March 2008

Identification of a chloride ion binding site in Na+/Cl -dependent transporters
journal, July 2007

  • Forrest, L. R.; Tavoulari, S.; Zhang, Y. -W.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 31
  • DOI: 10.1073/pnas.0705600104

The Origin of Allosteric Functional Modulation: Multiple Pre-existing Pathways
journal, August 2009

Computational modeling of the N-terminus of the human dopamine transporter and its interaction with PIP 2 -containing membranes : Modeling of DAT N-Terminus/PIP
journal, March 2015

  • Khelashvili, George; Doktorova, Milka; Sahai, Michelle A.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 83, Issue 5
  • DOI: 10.1002/prot.24792

PIP2 regulates psychostimulant behaviors through its interaction with a membrane protein
journal, June 2014

  • Hamilton, Peter J.; Belovich, Andrea N.; Khelashvili, George
  • Nature Chemical Biology, Vol. 10, Issue 7
  • DOI: 10.1038/nchembio.1545

De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder
journal, August 2013

  • Hamilton, P. J.; Campbell, N. G.; Sharma, S.
  • Molecular Psychiatry, Vol. 18, Issue 12
  • DOI: 10.1038/mp.2013.102

Missense dopamine transporter mutations associate with adult parkinsonism and ADHD
journal, June 2014

  • Hansen, Freja H.; Skjørringe, Tina; Yasmeen, Saiqa
  • Journal of Clinical Investigation, Vol. 124, Issue 7
  • DOI: 10.1172/JCI73778

Relationship between Conformational Changes in the Dopamine Transporter and Cocaine-Like Subjective Effects of Uptake Inhibitors
journal, October 2007

  • Loland, Claus J.; Desai, Rajeev I.; Zou, Mu-Fa
  • Molecular Pharmacology, Vol. 73, Issue 3
  • DOI: 10.1124/mol.107.039800

R-Modafinil (Armodafinil): A Unique Dopamine Uptake Inhibitor and Potential Medication for Psychostimulant Abuse
journal, September 2012

Scalable molecular dynamics with NAMD
journal, January 2005

  • Phillips, James C.; Braun, Rosemary; Wang, Wei
  • Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802
  • DOI: 10.1002/jcc.20289

Satisfying Hydrogen Bonding Potential in Proteins
journal, May 1994

  • McDonald, Ian K.; Thornton, Janet M.
  • Journal of Molecular Biology, Vol. 238, Issue 5
  • DOI: 10.1006/jmbi.1994.1334

A rapid, sensitive, and specific method for the determination of protein in dilute solution
journal, December 1973

VMD: Visual molecular dynamics
journal, February 1996

Coupled Global and Local Changes Direct Substrate Translocation by Neurotransmitter-Sodium Symporter Ortholog LeuT
journal, August 2013

Control of Ion Selectivity in LeuT: Two Na+ Binding Sites with Two Different Mechanisms
journal, March 2008

The Origin of Allosteric Functional Modulation: Multiple Pre-existing Pathways
journal, August 2009

The Role of Local Hydration and Hydrogen-Bonding Dynamics in Ion and Solute Release from Ion-Coupled Secondary Transporters
journal, March 2011

  • Zhao, Chunfeng; Noskov, Sergei Yu.
  • Biochemistry, Vol. 50, Issue 11
  • DOI: 10.1021/bi101454f

Improved Treatment of the Protein Backbone in Empirical Force Fields
journal, January 2004

  • MacKerell, Alexander D.; Feig, Michael; Brooks, Charles L.
  • Journal of the American Chemical Society, Vol. 126, Issue 3
  • DOI: 10.1021/ja036959e

Drosophila melanogaster: a novel animal model for the behavioral characterization of autism-associated mutations in the dopamine transporter gene
journal, November 2013

  • Hamilton, P. J.; Campbell, N. G.; Sharma, S.
  • Molecular Psychiatry, Vol. 18, Issue 12
  • DOI: 10.1038/mp.2013.157

Single-molecule dynamics of gating in a neurotransmitter transporter homologue
journal, May 2010

  • Zhao, Yongfang; Terry, Daniel; Shi, Lei
  • Nature, Vol. 465, Issue 7295
  • DOI: 10.1038/nature09057

Substrate-modulated gating dynamics in a Na+-coupled neurotransmitter transporter homologue
journal, April 2011

  • Zhao, Yongfang; Terry, Daniel S.; Shi, Lei
  • Nature, Vol. 474, Issue 7349
  • DOI: 10.1038/nature09971

X-ray structures of LeuT in substrate-free outward-open and apo inward-open states
journal, January 2012

Molecular signatures of G-protein-coupled receptors
journal, February 2013

  • Venkatakrishnan, A. J.; Deupi, Xavier; Lebon, Guillaume
  • Nature, Vol. 494, Issue 7436
  • DOI: 10.1038/nature11896

X-ray structure of dopamine transporter elucidates antidepressant mechanism
journal, September 2013

  • Penmatsa, Aravind; Wang, Kevin H.; Gouaux, Eric
  • Nature, Vol. 503, Issue 7474
  • DOI: 10.1038/nature12533

PIP2 regulates psychostimulant behaviors through its interaction with a membrane protein
journal, June 2014

  • Hamilton, Peter J.; Belovich, Andrea N.; Khelashvili, George
  • Nature Chemical Biology, Vol. 10, Issue 7
  • DOI: 10.1038/nchembio.1545

Ion/substrate-dependent conformational dynamics of a bacterial homolog of neurotransmitter:sodium symporters
journal, June 2010

  • Claxton, Derek P.; Quick, Matthias; Shi, Lei
  • Nature Structural & Molecular Biology, Vol. 17, Issue 7
  • DOI: 10.1038/nsmb.1854

Experimental conditions can obscure the second high-affinity site in LeuT
journal, January 2012

  • Quick, Matthias; Shi, Lei; Zehnpfennig, Britta
  • Nature Structural & Molecular Biology, Vol. 19, Issue 2
  • DOI: 10.1038/nsmb.2197

Generation of an activating Zn2+ switch in the dopamine transporter: Mutation of an intracellular tyrosine constitutively alters the conformational equilibrium of the transport cycle
journal, January 2002

  • Loland, C. J.; Norregaard, L.; Litman, T.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 3
  • DOI: 10.1073/pnas.032386299

Monitoring the function of membrane transport proteins in detergent-solubilized form
journal, February 2007

  • Quick, M.; Javitch, J. A.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 9
  • DOI: 10.1073/pnas.0609573104

Identification of a chloride ion binding site in Na+/Cl -dependent transporters
journal, July 2007

  • Forrest, L. R.; Tavoulari, S.; Zhang, Y. -W.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 31
  • DOI: 10.1073/pnas.0705600104

Mechanism for alternating access in neurotransmitter transporters
journal, July 2008

  • Forrest, L. R.; Zhang, Y. -W.; Jacobs, M. T.
  • Proceedings of the National Academy of Sciences, Vol. 105, Issue 30
  • DOI: 10.1073/pnas.0804659105

Two mechanisms of ion selectivity in protein binding sites
journal, November 2010

  • Yu, H.; Noskov, S. Y.; Roux, B.
  • Proceedings of the National Academy of Sciences, Vol. 107, Issue 47
  • DOI: 10.1073/pnas.1007150107

Chloride binding site of neurotransmitter sodium symporters
journal, May 2013

  • Kantcheva, A. K.; Quick, M.; Shi, L.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 21
  • DOI: 10.1073/pnas.1221279110

Identification of Intracellular Residues in the Dopamine Transporter Critical for Regulation of Transporter Conformation and Cocaine Binding
journal, November 2003

  • Loland, Claus Juul; Grånäs, Charlotta; Javitch, Jonathan A.
  • Journal of Biological Chemistry, Vol. 279, Issue 5
  • DOI: 10.1074/jbc.m304755200

State-dependent Conformations of the Translocation Pathway in the Tyrosine Transporter Tyt1, a Novel Neurotransmitter:Sodium Symporter from Fusobacterium nucleatum
journal, June 2006

  • Quick, Matthias; Yano, Hideaki; Goldberg, Naomi R.
  • Journal of Biological Chemistry, Vol. 281, Issue 36
  • DOI: 10.1074/jbc.m602438200

An Intracellular Interaction Network Regulates Conformational Transitions in the Dopamine Transporter
journal, April 2008

  • Kniazeff, Julie; Shi, Lei; Loland, Claus J.
  • Journal of Biological Chemistry, Vol. 283, Issue 25
  • DOI: 10.1074/jbc.m800475200
    Sort by:
    [ × clear filter / sort ]

    Works referencing / citing this record:

    A conserved leucine occupies the empty substrate site of LeuT in the Na+-free return state
    journal, May 2016

    • Malinauskaite, Lina; Said, Saida; Sahin, Caglanur
    • Nature Communications, Vol. 7, Issue 1
    • DOI: 10.1038/ncomms11673

    Transition metal ion FRET uncovers K+ regulation of a neurotransmitter/sodium symporter
    journal, September 2016

    • Billesbølle, Christian B.; Mortensen, Jonas S.; Sohail, Azmat
    • Nature Communications, Vol. 7, Issue 1
    • DOI: 10.1038/ncomms12755

    MHC class II complexes sample intermediate states along the peptide exchange pathway
    journal, November 2016

    • Wieczorek, Marek; Sticht, Jana; Stolzenberg, Sebastian
    • Nature Communications, Vol. 7, Issue 1
    • DOI: 10.1038/ncomms13224

    A partially-open inward-facing intermediate conformation of LeuT is associated with Na+ release and substrate transport
    journal, January 2018

    Bases of Bacterial Sodium Channel Selectivity Among Organic Cations
    journal, October 2019

    Locking Two Rigid-body Bundles in an Outward-Facing Conformation: The Ion-coupling Mechanism in a LeuT-fold Transporter
    journal, December 2019

    Competition between Li + and Na + in sodium transporters and receptors: Which Na + -Binding sites are “therapeutic” Li + targets?
    journal, January 2018

    • Dudev, Todor; Mazmanian, Karine; Lim, Carmay
    • Chemical Science, Vol. 9, Issue 17
    • DOI: 10.1039/c7sc05284g

    Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer
    journal, February 2017

    • Adhikary, Suraj; Deredge, Daniel J.; Nagarajan, Anu
    • Proceedings of the National Academy of Sciences, Vol. 114, Issue 10
    • DOI: 10.1073/pnas.1613293114

    Two Na + Sites Control Conformational Change in a Neurotransmitter Transporter Homolog
    journal, November 2015

    • Tavoulari, Sotiria; Margheritis, Eleonora; Nagarajan, Anu
    • Journal of Biological Chemistry, Vol. 291, Issue 3
    • DOI: 10.1074/jbc.m115.692012

    Conformational Dynamics on the Extracellular Side of LeuT Controlled by Na + and K + Ions and the Protonation State of Glu 290
    journal, July 2016

    • Khelashvili, George; Schmidt, Solveig Gaarde; Shi, Lei
    • Journal of Biological Chemistry, Vol. 291, Issue 38
    • DOI: 10.1074/jbc.m116.731455

    Modeling and Dynamics of the Inward-Facing State of a Na+/Cl− Dependent Neurotransmitter Transporter Homologue
    journal, August 2010

    Spontaneous Inward Opening of the Dopamine Transporter is Triggered by PIP2-Regulated Dynamics of the N-Terminus
    journal, February 2016

    Transition metal ion FRET uncovers K+ regulation of a neurotransmitter/sodium symporter
    journal, September 2016

    • Billesbølle, Christian B.; Mortensen, Jonas S.; Sohail, Azmat
    • Nature Communications, Vol. 7, Issue 1
    • DOI: 10.1038/ncomms12755

    MHC class II complexes sample intermediate states along the peptide exchange pathway
    journal, November 2016

    • Wieczorek, Marek; Sticht, Jana; Stolzenberg, Sebastian
    • Nature Communications, Vol. 7, Issue 1
    • DOI: 10.1038/ncomms13224

    A partially-open inward-facing intermediate conformation of LeuT is associated with Na+ release and substrate transport
    journal, January 2018

    Bases of Bacterial Sodium Channel Selectivity Among Organic Cations
    journal, October 2019

      Sort by:
      [ × clear filter / sort ]

      Similar Records in DOE PAGES and OSTI.GOV collections: