Lipid-dependent gating of a voltage-gated potassium channel

Hui Zheng, Weiran Liu, Lingyan Y. Anderson, Qiu Xing Jiang

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Recent studies hypothesized that phospholipids stabilize two voltage-sensing arginine residues of certain voltage-gated potassium channels in activated conformations. It remains unclear how lipids directly affect these channels. Here, by examining the conformations of the KvAP in different lipids, we showed that without voltage change, the voltage-sensor domains switched from the activated to the resting state when their surrounding lipids were changed from phospholipids to nonphospholipids. Such lipid-determined conformational change was coupled to the ion-conducting pore, suggesting that parallel to voltage gating, the channel is gated by its annular lipids. Our measurements recognized that the energetic cost of lipid-dependent gating approaches that of voltage gating, but kinetically it appears much slower. Our data support that a channel and its surrounding lipids together constitute a functional unit, and natural nonphospholipids such as cholesterol should exert strong effects on voltage-gated channels. Our first observation of lipid-dependent gating may have general implications to other membrane proteins.

Original languageEnglish (US)
Article number250
JournalNature Communications
Volume2
Issue number1
DOIs
StatePublished - 2011

Fingerprint

Voltage-Gated Potassium Channels
lipids
Lipids
electric potential
Electric potential
Conformations
Phospholipids
cholesterol
Arginine
Membrane Proteins
Cholesterol
Observation
Ions
membranes
proteins
costs
porosity
Costs and Cost Analysis
conduction
sensors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Zheng, H., Liu, W., Anderson, L. Y., & Jiang, Q. X. (2011). Lipid-dependent gating of a voltage-gated potassium channel. Nature Communications, 2(1), [250]. https://doi.org/10.1038/ncomms1254

Lipid-dependent gating of a voltage-gated potassium channel. / Zheng, Hui; Liu, Weiran; Anderson, Lingyan Y.; Jiang, Qiu Xing.

In: Nature Communications, Vol. 2, No. 1, 250, 2011.

Research output: Contribution to journalArticle

Zheng, Hui ; Liu, Weiran ; Anderson, Lingyan Y. ; Jiang, Qiu Xing. / Lipid-dependent gating of a voltage-gated potassium channel. In: Nature Communications. 2011 ; Vol. 2, No. 1.
@article{c35f4e87790e4ffc9ac6d118b096116a,
title = "Lipid-dependent gating of a voltage-gated potassium channel",
abstract = "Recent studies hypothesized that phospholipids stabilize two voltage-sensing arginine residues of certain voltage-gated potassium channels in activated conformations. It remains unclear how lipids directly affect these channels. Here, by examining the conformations of the KvAP in different lipids, we showed that without voltage change, the voltage-sensor domains switched from the activated to the resting state when their surrounding lipids were changed from phospholipids to nonphospholipids. Such lipid-determined conformational change was coupled to the ion-conducting pore, suggesting that parallel to voltage gating, the channel is gated by its annular lipids. Our measurements recognized that the energetic cost of lipid-dependent gating approaches that of voltage gating, but kinetically it appears much slower. Our data support that a channel and its surrounding lipids together constitute a functional unit, and natural nonphospholipids such as cholesterol should exert strong effects on voltage-gated channels. Our first observation of lipid-dependent gating may have general implications to other membrane proteins.",
author = "Hui Zheng and Weiran Liu and Anderson, {Lingyan Y.} and Jiang, {Qiu Xing}",
year = "2011",
doi = "10.1038/ncomms1254",
language = "English (US)",
volume = "2",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Lipid-dependent gating of a voltage-gated potassium channel

AU - Zheng, Hui

AU - Liu, Weiran

AU - Anderson, Lingyan Y.

AU - Jiang, Qiu Xing

PY - 2011

Y1 - 2011

N2 - Recent studies hypothesized that phospholipids stabilize two voltage-sensing arginine residues of certain voltage-gated potassium channels in activated conformations. It remains unclear how lipids directly affect these channels. Here, by examining the conformations of the KvAP in different lipids, we showed that without voltage change, the voltage-sensor domains switched from the activated to the resting state when their surrounding lipids were changed from phospholipids to nonphospholipids. Such lipid-determined conformational change was coupled to the ion-conducting pore, suggesting that parallel to voltage gating, the channel is gated by its annular lipids. Our measurements recognized that the energetic cost of lipid-dependent gating approaches that of voltage gating, but kinetically it appears much slower. Our data support that a channel and its surrounding lipids together constitute a functional unit, and natural nonphospholipids such as cholesterol should exert strong effects on voltage-gated channels. Our first observation of lipid-dependent gating may have general implications to other membrane proteins.

AB - Recent studies hypothesized that phospholipids stabilize two voltage-sensing arginine residues of certain voltage-gated potassium channels in activated conformations. It remains unclear how lipids directly affect these channels. Here, by examining the conformations of the KvAP in different lipids, we showed that without voltage change, the voltage-sensor domains switched from the activated to the resting state when their surrounding lipids were changed from phospholipids to nonphospholipids. Such lipid-determined conformational change was coupled to the ion-conducting pore, suggesting that parallel to voltage gating, the channel is gated by its annular lipids. Our measurements recognized that the energetic cost of lipid-dependent gating approaches that of voltage gating, but kinetically it appears much slower. Our data support that a channel and its surrounding lipids together constitute a functional unit, and natural nonphospholipids such as cholesterol should exert strong effects on voltage-gated channels. Our first observation of lipid-dependent gating may have general implications to other membrane proteins.

UR - http://www.scopus.com/inward/record.url?scp=79953236295&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953236295&partnerID=8YFLogxK

U2 - 10.1038/ncomms1254

DO - 10.1038/ncomms1254

M3 - Article

VL - 2

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 250

ER -