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KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting

Standard

KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting. / Wrobel, Eva; Rothenberg, Ina; Krisp, Christoph; Hundt, Franziska; Fraenzel, Benjamin; Eckey, Karina; Linders, Joannes T M; Gallacher, David J; Towart, Rob; Pott, Lutz; Pusch, Michael; Yang, Tao; Roden, Dan M; Kurata, Harley T; Schulze-Bahr, Eric; Strutz-Seebohm, Nathalie; Wolters, Dirk; Seebohm, Guiscard.

In: NAT COMMUN, Vol. 7, 12.10.2016, p. 12795.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wrobel, E, Rothenberg, I, Krisp, C, Hundt, F, Fraenzel, B, Eckey, K, Linders, JTM, Gallacher, DJ, Towart, R, Pott, L, Pusch, M, Yang, T, Roden, DM, Kurata, HT, Schulze-Bahr, E, Strutz-Seebohm, N, Wolters, D & Seebohm, G 2016, 'KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting', NAT COMMUN, vol. 7, pp. 12795. https://doi.org/10.1038/ncomms12795

APA

Wrobel, E., Rothenberg, I., Krisp, C., Hundt, F., Fraenzel, B., Eckey, K., Linders, J. T. M., Gallacher, D. J., Towart, R., Pott, L., Pusch, M., Yang, T., Roden, D. M., Kurata, H. T., Schulze-Bahr, E., Strutz-Seebohm, N., Wolters, D., & Seebohm, G. (2016). KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting. NAT COMMUN, 7, 12795. https://doi.org/10.1038/ncomms12795

Vancouver

Wrobel E, Rothenberg I, Krisp C, Hundt F, Fraenzel B, Eckey K et al. KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting. NAT COMMUN. 2016 Oct 12;7:12795. https://doi.org/10.1038/ncomms12795

Bibtex

@article{8e96512895c74149b1b0208e75c2b204,
title = "KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting",
abstract = "Most small-molecule inhibitors of voltage-gated ion channels display poor subtype specificity because they bind to highly conserved residues located in the channel's central cavity. Using a combined approach of scanning mutagenesis, electrophysiology, chemical ligand modification, chemical cross-linking, MS/MS-analyses and molecular modelling, we provide evidence for the binding site for adamantane derivatives and their putative access pathway in Kv7.1/KCNE1 channels. The adamantane compounds, exemplified by JNJ303, are highly potent gating modifiers that bind to fenestrations that become available when KCNE1 accessory subunits are bound to Kv7.1 channels. This mode of regulation by auxiliary subunits may facilitate the future development of potent and highly subtype-specific Kv channel inhibitors.",
keywords = "Journal Article",
author = "Eva Wrobel and Ina Rothenberg and Christoph Krisp and Franziska Hundt and Benjamin Fraenzel and Karina Eckey and Linders, {Joannes T M} and Gallacher, {David J} and Rob Towart and Lutz Pott and Michael Pusch and Tao Yang and Roden, {Dan M} and Kurata, {Harley T} and Eric Schulze-Bahr and Nathalie Strutz-Seebohm and Dirk Wolters and Guiscard Seebohm",
year = "2016",
month = oct,
day = "12",
doi = "10.1038/ncomms12795",
language = "English",
volume = "7",
pages = "12795",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting

AU - Wrobel, Eva

AU - Rothenberg, Ina

AU - Krisp, Christoph

AU - Hundt, Franziska

AU - Fraenzel, Benjamin

AU - Eckey, Karina

AU - Linders, Joannes T M

AU - Gallacher, David J

AU - Towart, Rob

AU - Pott, Lutz

AU - Pusch, Michael

AU - Yang, Tao

AU - Roden, Dan M

AU - Kurata, Harley T

AU - Schulze-Bahr, Eric

AU - Strutz-Seebohm, Nathalie

AU - Wolters, Dirk

AU - Seebohm, Guiscard

PY - 2016/10/12

Y1 - 2016/10/12

N2 - Most small-molecule inhibitors of voltage-gated ion channels display poor subtype specificity because they bind to highly conserved residues located in the channel's central cavity. Using a combined approach of scanning mutagenesis, electrophysiology, chemical ligand modification, chemical cross-linking, MS/MS-analyses and molecular modelling, we provide evidence for the binding site for adamantane derivatives and their putative access pathway in Kv7.1/KCNE1 channels. The adamantane compounds, exemplified by JNJ303, are highly potent gating modifiers that bind to fenestrations that become available when KCNE1 accessory subunits are bound to Kv7.1 channels. This mode of regulation by auxiliary subunits may facilitate the future development of potent and highly subtype-specific Kv channel inhibitors.

AB - Most small-molecule inhibitors of voltage-gated ion channels display poor subtype specificity because they bind to highly conserved residues located in the channel's central cavity. Using a combined approach of scanning mutagenesis, electrophysiology, chemical ligand modification, chemical cross-linking, MS/MS-analyses and molecular modelling, we provide evidence for the binding site for adamantane derivatives and their putative access pathway in Kv7.1/KCNE1 channels. The adamantane compounds, exemplified by JNJ303, are highly potent gating modifiers that bind to fenestrations that become available when KCNE1 accessory subunits are bound to Kv7.1 channels. This mode of regulation by auxiliary subunits may facilitate the future development of potent and highly subtype-specific Kv channel inhibitors.

KW - Journal Article

U2 - 10.1038/ncomms12795

DO - 10.1038/ncomms12795

M3 - SCORING: Journal article

C2 - 27731317

VL - 7

SP - 12795

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

ER -