The Environment Shapes the Inner Vestibule of LeuT

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Standard

The Environment Shapes the Inner Vestibule of LeuT. / Sohail, Azmat; Jayaraman, Kumaresan; Venkatesan, Santhoshkannan; Gotfryd, Kamil; Daerr, Markus; Gether, Ulrik; Loland, Claus J; Wanner, Klaus T; Freissmuth, Michael; Sitte, Harald H; Sandtner, Walter; Stockner, Thomas.

I: PLoS Computational Biology, Bind 12, Nr. 11, e1005197, 11.2016.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Sohail, A, Jayaraman, K, Venkatesan, S, Gotfryd, K, Daerr, M, Gether, U, Loland, CJ, Wanner, KT, Freissmuth, M, Sitte, HH, Sandtner, W & Stockner, T 2016, 'The Environment Shapes the Inner Vestibule of LeuT', PLoS Computational Biology, bind 12, nr. 11, e1005197. https://doi.org/10.1371/journal.pcbi.1005197

APA

Sohail, A., Jayaraman, K., Venkatesan, S., Gotfryd, K., Daerr, M., Gether, U., ... Stockner, T. (2016). The Environment Shapes the Inner Vestibule of LeuT. PLoS Computational Biology, 12(11), [e1005197]. https://doi.org/10.1371/journal.pcbi.1005197

Vancouver

Sohail A, Jayaraman K, Venkatesan S, Gotfryd K, Daerr M, Gether U o.a. The Environment Shapes the Inner Vestibule of LeuT. PLoS Computational Biology. 2016 nov;12(11). e1005197. https://doi.org/10.1371/journal.pcbi.1005197

Author

Sohail, Azmat ; Jayaraman, Kumaresan ; Venkatesan, Santhoshkannan ; Gotfryd, Kamil ; Daerr, Markus ; Gether, Ulrik ; Loland, Claus J ; Wanner, Klaus T ; Freissmuth, Michael ; Sitte, Harald H ; Sandtner, Walter ; Stockner, Thomas. / The Environment Shapes the Inner Vestibule of LeuT. I: PLoS Computational Biology. 2016 ; Bind 12, Nr. 11.

Bibtex

@article{81555015f13a439e840d5606d5cd330c,
title = "The Environment Shapes the Inner Vestibule of LeuT",
abstract = "Human neurotransmitter transporters are found in the nervous system terminating synaptic signals by rapid removal of neurotransmitter molecules from the synaptic cleft. The homologous transporter LeuT, found in Aquifex aeolicus, was crystallized in different conformations. Here, we investigated the inward-open state of LeuT. We compared LeuT in membranes and micelles using molecular dynamics simulations and lanthanide-based resonance energy transfer (LRET). Simulations of micelle-solubilized LeuT revealed a stable and widely open inward-facing conformation. However, this conformation was unstable in a membrane environment. The helix dipole and the charged amino acid of the first transmembrane helix (TM1A) partitioned out of the hydrophobic membrane core. Free energy calculations showed that movement of TM1A by 0.30 nm was driven by a free energy difference of ~15 kJ/mol. Distance measurements by LRET showed TM1A movements, consistent with the simulations, confirming a substantially different inward-open conformation in lipid bilayer from that inferred from the crystal structure.",
author = "Azmat Sohail and Kumaresan Jayaraman and Santhoshkannan Venkatesan and Kamil Gotfryd and Markus Daerr and Ulrik Gether and Loland, {Claus J} and Wanner, {Klaus T} and Michael Freissmuth and Sitte, {Harald H} and Walter Sandtner and Thomas Stockner",
year = "2016",
month = "11",
doi = "10.1371/journal.pcbi.1005197",
language = "English",
volume = "12",
journal = "P L o S Computational Biology (Online)",
issn = "1553-7358",
publisher = "Public Library of Science",
number = "11",

}

RIS

TY - JOUR

T1 - The Environment Shapes the Inner Vestibule of LeuT

AU - Sohail, Azmat

AU - Jayaraman, Kumaresan

AU - Venkatesan, Santhoshkannan

AU - Gotfryd, Kamil

AU - Daerr, Markus

AU - Gether, Ulrik

AU - Loland, Claus J

AU - Wanner, Klaus T

AU - Freissmuth, Michael

AU - Sitte, Harald H

AU - Sandtner, Walter

AU - Stockner, Thomas

PY - 2016/11

Y1 - 2016/11

N2 - Human neurotransmitter transporters are found in the nervous system terminating synaptic signals by rapid removal of neurotransmitter molecules from the synaptic cleft. The homologous transporter LeuT, found in Aquifex aeolicus, was crystallized in different conformations. Here, we investigated the inward-open state of LeuT. We compared LeuT in membranes and micelles using molecular dynamics simulations and lanthanide-based resonance energy transfer (LRET). Simulations of micelle-solubilized LeuT revealed a stable and widely open inward-facing conformation. However, this conformation was unstable in a membrane environment. The helix dipole and the charged amino acid of the first transmembrane helix (TM1A) partitioned out of the hydrophobic membrane core. Free energy calculations showed that movement of TM1A by 0.30 nm was driven by a free energy difference of ~15 kJ/mol. Distance measurements by LRET showed TM1A movements, consistent with the simulations, confirming a substantially different inward-open conformation in lipid bilayer from that inferred from the crystal structure.

AB - Human neurotransmitter transporters are found in the nervous system terminating synaptic signals by rapid removal of neurotransmitter molecules from the synaptic cleft. The homologous transporter LeuT, found in Aquifex aeolicus, was crystallized in different conformations. Here, we investigated the inward-open state of LeuT. We compared LeuT in membranes and micelles using molecular dynamics simulations and lanthanide-based resonance energy transfer (LRET). Simulations of micelle-solubilized LeuT revealed a stable and widely open inward-facing conformation. However, this conformation was unstable in a membrane environment. The helix dipole and the charged amino acid of the first transmembrane helix (TM1A) partitioned out of the hydrophobic membrane core. Free energy calculations showed that movement of TM1A by 0.30 nm was driven by a free energy difference of ~15 kJ/mol. Distance measurements by LRET showed TM1A movements, consistent with the simulations, confirming a substantially different inward-open conformation in lipid bilayer from that inferred from the crystal structure.

U2 - 10.1371/journal.pcbi.1005197

DO - 10.1371/journal.pcbi.1005197

M3 - Journal article

VL - 12

JO - P L o S Computational Biology (Online)

JF - P L o S Computational Biology (Online)

SN - 1553-7358

IS - 11

M1 - e1005197

ER -

ID: 168931706