Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels

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

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Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels. / Pless, Stephan Alexander; Galpin, Jason D; Niciforovic, Ana P; Kurata, Harley T; Ahern, Christopher A.

In: eLife, Vol. 2, 2013, p. e01289.

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

Harvard

Pless, SA, Galpin, JD, Niciforovic, AP, Kurata, HT & Ahern, CA 2013, 'Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels', eLife, vol. 2, pp. e01289. https://doi.org/10.7554/eLife.01289

APA

Pless, S. A., Galpin, J. D., Niciforovic, A. P., Kurata, H. T., & Ahern, C. A. (2013). Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels. eLife, 2, e01289. https://doi.org/10.7554/eLife.01289

Vancouver

Pless SA, Galpin JD, Niciforovic AP, Kurata HT, Ahern CA. Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels. eLife. 2013;2:e01289. https://doi.org/10.7554/eLife.01289

Author

Pless, Stephan Alexander ; Galpin, Jason D ; Niciforovic, Ana P ; Kurata, Harley T ; Ahern, Christopher A. / Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels. In: eLife. 2013 ; Vol. 2. pp. e01289.

Bibtex

@article{219cc1498bea442e8135a4f8e9e00ac9,
title = "Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels",
abstract = "Voltage-gated potassium (Kv) channels enable potassium efflux and membrane repolarization in excitable tissues. Many Kv channels undergo a progressive loss of ion conductance in the presence of a prolonged voltage stimulus, termed slow inactivation, but the atomic determinants that regulate the kinetics of this process remain obscure. Using a combination of synthetic amino acid analogs and concatenated channel subunits we establish two H-bonds near the extracellular surface of the channel that endow Kv channels with a mechanism to time the entry into slow inactivation: an intra-subunit H-bond between Asp447 and Trp434 and an inter-subunit H-bond connecting Tyr445 to Thr439. Breaking of either interaction triggers slow inactivation by means of a local disruption in the selectivity filter, while severing the Tyr445-Thr439 H-bond is likely to communicate this conformational change to the adjacent subunit(s). DOI: http://dx.doi.org/10.7554/eLife.01289.001.",
author = "Pless, {Stephan Alexander} and Galpin, {Jason D} and Niciforovic, {Ana P} and Kurata, {Harley T} and Ahern, {Christopher A}",
year = "2013",
doi = "10.7554/eLife.01289",
language = "English",
volume = "2",
pages = "e01289",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels

AU - Pless, Stephan Alexander

AU - Galpin, Jason D

AU - Niciforovic, Ana P

AU - Kurata, Harley T

AU - Ahern, Christopher A

PY - 2013

Y1 - 2013

N2 - Voltage-gated potassium (Kv) channels enable potassium efflux and membrane repolarization in excitable tissues. Many Kv channels undergo a progressive loss of ion conductance in the presence of a prolonged voltage stimulus, termed slow inactivation, but the atomic determinants that regulate the kinetics of this process remain obscure. Using a combination of synthetic amino acid analogs and concatenated channel subunits we establish two H-bonds near the extracellular surface of the channel that endow Kv channels with a mechanism to time the entry into slow inactivation: an intra-subunit H-bond between Asp447 and Trp434 and an inter-subunit H-bond connecting Tyr445 to Thr439. Breaking of either interaction triggers slow inactivation by means of a local disruption in the selectivity filter, while severing the Tyr445-Thr439 H-bond is likely to communicate this conformational change to the adjacent subunit(s). DOI: http://dx.doi.org/10.7554/eLife.01289.001.

AB - Voltage-gated potassium (Kv) channels enable potassium efflux and membrane repolarization in excitable tissues. Many Kv channels undergo a progressive loss of ion conductance in the presence of a prolonged voltage stimulus, termed slow inactivation, but the atomic determinants that regulate the kinetics of this process remain obscure. Using a combination of synthetic amino acid analogs and concatenated channel subunits we establish two H-bonds near the extracellular surface of the channel that endow Kv channels with a mechanism to time the entry into slow inactivation: an intra-subunit H-bond between Asp447 and Trp434 and an inter-subunit H-bond connecting Tyr445 to Thr439. Breaking of either interaction triggers slow inactivation by means of a local disruption in the selectivity filter, while severing the Tyr445-Thr439 H-bond is likely to communicate this conformational change to the adjacent subunit(s). DOI: http://dx.doi.org/10.7554/eLife.01289.001.

U2 - 10.7554/eLife.01289

DO - 10.7554/eLife.01289

M3 - Journal article

C2 - 24327560

VL - 2

SP - e01289

JO - eLife

JF - eLife

SN - 2050-084X

ER -

ID: 122597413