A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel

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

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A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel. / Pless, Stephan Alexander; Niciforovic, Ana P; Galpin, Jason D; Nunez, John-Jose; Kurata, Harley T; Ahern, Christopher A.

In: Nature Communications, Vol. 4, 2013, p. 1784.

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

Harvard

Pless, SA, Niciforovic, AP, Galpin, JD, Nunez, J-J, Kurata, HT & Ahern, CA 2013, 'A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel', Nature Communications, vol. 4, pp. 1784. https://doi.org/10.1038/ncomms2761

APA

Pless, S. A., Niciforovic, A. P., Galpin, J. D., Nunez, J-J., Kurata, H. T., & Ahern, C. A. (2013). A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel. Nature Communications, 4, 1784. https://doi.org/10.1038/ncomms2761

Vancouver

Pless SA, Niciforovic AP, Galpin JD, Nunez J-J, Kurata HT, Ahern CA. A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel. Nature Communications. 2013;4:1784. https://doi.org/10.1038/ncomms2761

Author

Pless, Stephan Alexander ; Niciforovic, Ana P ; Galpin, Jason D ; Nunez, John-Jose ; Kurata, Harley T ; Ahern, Christopher A. / A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel. In: Nature Communications. 2013 ; Vol. 4. pp. 1784.

Bibtex

@article{44b4932d2b524cd8a52fdae7f1f18fb6,
title = "A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel",
abstract = "Voltage-gated potassium channels elicit membrane hyperpolarization through voltage-sensor domains that regulate the conductive status of the pore domain. To better understand the inherent basis for the open-closed equilibrium in these channels, we undertook an atomistic scan using synthetic fluorinated derivatives of aromatic residues previously implicated in the gating of Shaker potassium channels. Here we show that stepwise dispersion of the negative electrostatic surface potential of only one site, Phe481, stabilizes the channel open state. Furthermore, these data suggest that this apparent stabilization is the consequence of the amelioration of an inherently repulsive open-state interaction between the partial negative charge on the face of Phe481 and a highly co-evolved acidic side chain, Glu395, and this interaction is potentially modulated through the Tyr485 hydroxyl. We propose that the intrinsic open-state destabilization via aromatic repulsion represents a new mechanism by which ion channels, and likely other proteins, fine-tune conformational equilibria.",
keywords = "Amino Acid Sequence, Animals, Glutamic Acid, Halogenation, Ion Channel Gating, Kinetics, Models, Biological, Models, Molecular, Molecular Sequence Data, Mutant Proteins, Mutation, Phenylalanine, Potassium Channels, Voltage-Gated, Protein Binding, Static Electricity, Statistics as Topic, Surface Properties, Xenopus laevis",
author = "Pless, {Stephan Alexander} and Niciforovic, {Ana P} and Galpin, {Jason D} and John-Jose Nunez and Kurata, {Harley T} and Ahern, {Christopher A}",
year = "2013",
doi = "10.1038/ncomms2761",
language = "English",
volume = "4",
pages = "1784",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel

AU - Pless, Stephan Alexander

AU - Niciforovic, Ana P

AU - Galpin, Jason D

AU - Nunez, John-Jose

AU - Kurata, Harley T

AU - Ahern, Christopher A

PY - 2013

Y1 - 2013

N2 - Voltage-gated potassium channels elicit membrane hyperpolarization through voltage-sensor domains that regulate the conductive status of the pore domain. To better understand the inherent basis for the open-closed equilibrium in these channels, we undertook an atomistic scan using synthetic fluorinated derivatives of aromatic residues previously implicated in the gating of Shaker potassium channels. Here we show that stepwise dispersion of the negative electrostatic surface potential of only one site, Phe481, stabilizes the channel open state. Furthermore, these data suggest that this apparent stabilization is the consequence of the amelioration of an inherently repulsive open-state interaction between the partial negative charge on the face of Phe481 and a highly co-evolved acidic side chain, Glu395, and this interaction is potentially modulated through the Tyr485 hydroxyl. We propose that the intrinsic open-state destabilization via aromatic repulsion represents a new mechanism by which ion channels, and likely other proteins, fine-tune conformational equilibria.

AB - Voltage-gated potassium channels elicit membrane hyperpolarization through voltage-sensor domains that regulate the conductive status of the pore domain. To better understand the inherent basis for the open-closed equilibrium in these channels, we undertook an atomistic scan using synthetic fluorinated derivatives of aromatic residues previously implicated in the gating of Shaker potassium channels. Here we show that stepwise dispersion of the negative electrostatic surface potential of only one site, Phe481, stabilizes the channel open state. Furthermore, these data suggest that this apparent stabilization is the consequence of the amelioration of an inherently repulsive open-state interaction between the partial negative charge on the face of Phe481 and a highly co-evolved acidic side chain, Glu395, and this interaction is potentially modulated through the Tyr485 hydroxyl. We propose that the intrinsic open-state destabilization via aromatic repulsion represents a new mechanism by which ion channels, and likely other proteins, fine-tune conformational equilibria.

KW - Amino Acid Sequence

KW - Animals

KW - Glutamic Acid

KW - Halogenation

KW - Ion Channel Gating

KW - Kinetics

KW - Models, Biological

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Mutant Proteins

KW - Mutation

KW - Phenylalanine

KW - Potassium Channels, Voltage-Gated

KW - Protein Binding

KW - Static Electricity

KW - Statistics as Topic

KW - Surface Properties

KW - Xenopus laevis

U2 - 10.1038/ncomms2761

DO - 10.1038/ncomms2761

M3 - Journal article

C2 - 23653196

VL - 4

SP - 1784

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -

ID: 122597442