Chloride binding site of neurotransmitter sodium symporters

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Standard

Chloride binding site of neurotransmitter sodium symporters. / Kantcheva, Adriana Krassimirova; Quick, Matthias; Shi, Lei; Winther, Anne-Marie Lund; Stolzenberg, Sebastian; Weinstein, Harel; Javitch, Jonathan A.; Nissen, Poul.

I: Proceedings of the National Academy of Sciences of the United States of America, Bind 110, Nr. 21, 21.05.2013, s. 8489-8494.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Kantcheva, AK, Quick, M, Shi, L, Winther, A-ML, Stolzenberg, S, Weinstein, H, Javitch, JA & Nissen, P 2013, 'Chloride binding site of neurotransmitter sodium symporters', Proceedings of the National Academy of Sciences of the United States of America, bind 110, nr. 21, s. 8489-8494. https://doi.org/10.1073/pnas.1221279110

APA

Kantcheva, A. K., Quick, M., Shi, L., Winther, A-M. L., Stolzenberg, S., Weinstein, H., ... Nissen, P. (2013). Chloride binding site of neurotransmitter sodium symporters. Proceedings of the National Academy of Sciences of the United States of America, 110(21), 8489-8494. https://doi.org/10.1073/pnas.1221279110

CBE

Kantcheva AK, Quick M, Shi L, Winther A-ML, Stolzenberg S, Weinstein H, Javitch JA, Nissen P. 2013. Chloride binding site of neurotransmitter sodium symporters. Proceedings of the National Academy of Sciences of the United States of America. 110(21):8489-8494. https://doi.org/10.1073/pnas.1221279110

MLA

Kantcheva, Adriana Krassimirova o.a.. "Chloride binding site of neurotransmitter sodium symporters". Proceedings of the National Academy of Sciences of the United States of America. 2013, 110(21). 8489-8494. https://doi.org/10.1073/pnas.1221279110

Vancouver

Kantcheva AK, Quick M, Shi L, Winther A-ML, Stolzenberg S, Weinstein H o.a. Chloride binding site of neurotransmitter sodium symporters. Proceedings of the National Academy of Sciences of the United States of America. 2013 maj 21;110(21):8489-8494. https://doi.org/10.1073/pnas.1221279110

Author

Kantcheva, Adriana Krassimirova ; Quick, Matthias ; Shi, Lei ; Winther, Anne-Marie Lund ; Stolzenberg, Sebastian ; Weinstein, Harel ; Javitch, Jonathan A. ; Nissen, Poul. / Chloride binding site of neurotransmitter sodium symporters. I: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Bind 110, Nr. 21. s. 8489-8494.

Bibtex

@article{a104a021ac024ffe97c4cca23cc18f9c,
title = "Chloride binding site of neurotransmitter sodium symporters",
abstract = "Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs have a serine. The LeuT-E290S mutant displays chloride-dependent activity. We show that, in LeuT-E290S cocrystallized with bromide or chloride, the anion is coordinated by side chain hydroxyls from Tyr47, Ser290, and Thr254 and the side chain amide of Gln250. The bound anion and the nearby sodium ion in the Na1 site organize a connection between their coordinating residues and the extracellular gate of LeuT through a continuous H-bond network. The specific insights from the structures, combined with results from substrate binding studies and molecular dynamics simulations, reveal an anion-dependent occlusion mechanism for NSS and shed light on the functional role of chloride binding",
keywords = "membrane transport, X-ray crystallography, SLC6, antidepressant, psychostimulant",
author = "Kantcheva, {Adriana Krassimirova} and Matthias Quick and Lei Shi and Winther, {Anne-Marie Lund} and Sebastian Stolzenberg and Harel Weinstein and Javitch, {Jonathan A.} and Poul Nissen",
year = "2013",
month = "5",
day = "21",
doi = "10.1073/pnas.1221279110",
language = "English",
volume = "110",
pages = "8489--8494",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "21",

}

RIS

TY - JOUR

T1 - Chloride binding site of neurotransmitter sodium symporters

AU - Kantcheva, Adriana Krassimirova

AU - Quick, Matthias

AU - Shi, Lei

AU - Winther, Anne-Marie Lund

AU - Stolzenberg, Sebastian

AU - Weinstein, Harel

AU - Javitch, Jonathan A.

AU - Nissen, Poul

PY - 2013/5/21

Y1 - 2013/5/21

N2 - Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs have a serine. The LeuT-E290S mutant displays chloride-dependent activity. We show that, in LeuT-E290S cocrystallized with bromide or chloride, the anion is coordinated by side chain hydroxyls from Tyr47, Ser290, and Thr254 and the side chain amide of Gln250. The bound anion and the nearby sodium ion in the Na1 site organize a connection between their coordinating residues and the extracellular gate of LeuT through a continuous H-bond network. The specific insights from the structures, combined with results from substrate binding studies and molecular dynamics simulations, reveal an anion-dependent occlusion mechanism for NSS and shed light on the functional role of chloride binding

AB - Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT are chloride-independent but contain an acidic residue (Glu290 in LeuT) at a site where eukaryotic NSSs have a serine. The LeuT-E290S mutant displays chloride-dependent activity. We show that, in LeuT-E290S cocrystallized with bromide or chloride, the anion is coordinated by side chain hydroxyls from Tyr47, Ser290, and Thr254 and the side chain amide of Gln250. The bound anion and the nearby sodium ion in the Na1 site organize a connection between their coordinating residues and the extracellular gate of LeuT through a continuous H-bond network. The specific insights from the structures, combined with results from substrate binding studies and molecular dynamics simulations, reveal an anion-dependent occlusion mechanism for NSS and shed light on the functional role of chloride binding

KW - membrane transport

KW - X-ray crystallography

KW - SLC6

KW - antidepressant

KW - psychostimulant

U2 - 10.1073/pnas.1221279110

DO - 10.1073/pnas.1221279110

M3 - Journal article

C2 - 23641004

VL - 110

SP - 8489

EP - 8494

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 21

ER -