Structural basis of slow activation gating in the cardiac IKs channel complex

Research output: Contribution to journalJournal articleResearchpeer-review

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Structural basis of slow activation gating in the cardiac IKs channel complex. / Strutz-Seebohm, Nathalie; Pusch, Michael; Wolf, Steffen; Stoll, Raphael; Tapken, Daniel; Gerwert, Klaus; Attali, Bernard; Seebohm, Guiscard.

In: Cellular Physiology and Biochemistry, Vol. 27, No. 5, 2011, p. 443-452.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Strutz-Seebohm, N, Pusch, M, Wolf, S, Stoll, R, Tapken, D, Gerwert, K, Attali, B & Seebohm, G 2011, 'Structural basis of slow activation gating in the cardiac IKs channel complex', Cellular Physiology and Biochemistry, vol. 27, no. 5, pp. 443-452. https://doi.org/10.1159/000329965

APA

Strutz-Seebohm, N., Pusch, M., Wolf, S., Stoll, R., Tapken, D., Gerwert, K., ... Seebohm, G. (2011). Structural basis of slow activation gating in the cardiac IKs channel complex. Cellular Physiology and Biochemistry, 27(5), 443-452. https://doi.org/10.1159/000329965

Vancouver

Strutz-Seebohm N, Pusch M, Wolf S, Stoll R, Tapken D, Gerwert K et al. Structural basis of slow activation gating in the cardiac IKs channel complex. Cellular Physiology and Biochemistry. 2011;27(5):443-452. https://doi.org/10.1159/000329965

Author

Strutz-Seebohm, Nathalie ; Pusch, Michael ; Wolf, Steffen ; Stoll, Raphael ; Tapken, Daniel ; Gerwert, Klaus ; Attali, Bernard ; Seebohm, Guiscard. / Structural basis of slow activation gating in the cardiac IKs channel complex. In: Cellular Physiology and Biochemistry. 2011 ; Vol. 27, No. 5. pp. 443-452.

Bibtex

@article{72ca19a413ed4a3489e28502e5160acc,
title = "Structural basis of slow activation gating in the cardiac IKs channel complex",
abstract = "Accessory {\ss}-subunits of the KCNE gene family modulate the function of various cation channel a-subunits by the formation of heteromultimers. Among the most dramatic changes of biophysical properties of a voltage-gated channel by KCNEs are the effects of KCNE1 on KCNQ1 channels. KCNQ1 and KCNE1 are believed to form nativeI(Ks) channels. Here, we characterize molecular determinants of KCNE1 interaction with KCNQ1 channels by scanning mutagenesis, double mutant cycle analysis, and molecular dynamics simulations. Our findings suggest that KCNE1 binds to the outer face of the KCNQ1 channel pore domain, modifies interactions between voltage sensor, S4-S5 linker and the pore domain, leading to structural modifications of the selectivity filter and voltage sensor domain. Molecular dynamics simulations suggest a stable interaction of the KCNE1 transmembrane a-helix with the pore domain S5/S6 and part of the voltage sensor domain S4 of KCNQ1 in a putative pre-open channel state. Formation of this state may induce slow activation gating, the pivotal characteristic of native cardiac I(Ks) channels. This new KCNQ1-KCNE1 model may become useful for dynamic modeling of disease-associated mutant I(Ks) channels.",
keywords = "The Faculty of Pharmaceutical Sciences",
author = "Nathalie Strutz-Seebohm and Michael Pusch and Steffen Wolf and Raphael Stoll and Daniel Tapken and Klaus Gerwert and Bernard Attali and Guiscard Seebohm",
note = "Key Words: KCNQ1/KCNE1, structure, model",
year = "2011",
doi = "10.1159/000329965",
language = "English",
volume = "27",
pages = "443--452",
journal = "Cellular Physiology and Biochemistry",
issn = "1015-8987",
publisher = "S Karger AG",
number = "5",

}

RIS

TY - JOUR

T1 - Structural basis of slow activation gating in the cardiac IKs channel complex

AU - Strutz-Seebohm, Nathalie

AU - Pusch, Michael

AU - Wolf, Steffen

AU - Stoll, Raphael

AU - Tapken, Daniel

AU - Gerwert, Klaus

AU - Attali, Bernard

AU - Seebohm, Guiscard

N1 - Key Words: KCNQ1/KCNE1, structure, model

PY - 2011

Y1 - 2011

N2 - Accessory ß-subunits of the KCNE gene family modulate the function of various cation channel a-subunits by the formation of heteromultimers. Among the most dramatic changes of biophysical properties of a voltage-gated channel by KCNEs are the effects of KCNE1 on KCNQ1 channels. KCNQ1 and KCNE1 are believed to form nativeI(Ks) channels. Here, we characterize molecular determinants of KCNE1 interaction with KCNQ1 channels by scanning mutagenesis, double mutant cycle analysis, and molecular dynamics simulations. Our findings suggest that KCNE1 binds to the outer face of the KCNQ1 channel pore domain, modifies interactions between voltage sensor, S4-S5 linker and the pore domain, leading to structural modifications of the selectivity filter and voltage sensor domain. Molecular dynamics simulations suggest a stable interaction of the KCNE1 transmembrane a-helix with the pore domain S5/S6 and part of the voltage sensor domain S4 of KCNQ1 in a putative pre-open channel state. Formation of this state may induce slow activation gating, the pivotal characteristic of native cardiac I(Ks) channels. This new KCNQ1-KCNE1 model may become useful for dynamic modeling of disease-associated mutant I(Ks) channels.

AB - Accessory ß-subunits of the KCNE gene family modulate the function of various cation channel a-subunits by the formation of heteromultimers. Among the most dramatic changes of biophysical properties of a voltage-gated channel by KCNEs are the effects of KCNE1 on KCNQ1 channels. KCNQ1 and KCNE1 are believed to form nativeI(Ks) channels. Here, we characterize molecular determinants of KCNE1 interaction with KCNQ1 channels by scanning mutagenesis, double mutant cycle analysis, and molecular dynamics simulations. Our findings suggest that KCNE1 binds to the outer face of the KCNQ1 channel pore domain, modifies interactions between voltage sensor, S4-S5 linker and the pore domain, leading to structural modifications of the selectivity filter and voltage sensor domain. Molecular dynamics simulations suggest a stable interaction of the KCNE1 transmembrane a-helix with the pore domain S5/S6 and part of the voltage sensor domain S4 of KCNQ1 in a putative pre-open channel state. Formation of this state may induce slow activation gating, the pivotal characteristic of native cardiac I(Ks) channels. This new KCNQ1-KCNE1 model may become useful for dynamic modeling of disease-associated mutant I(Ks) channels.

KW - The Faculty of Pharmaceutical Sciences

U2 - 10.1159/000329965

DO - 10.1159/000329965

M3 - Journal article

VL - 27

SP - 443

EP - 452

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

SN - 1015-8987

IS - 5

ER -

ID: 38384443