The Voltage-Dependent Deactivation of the KvAP Channel Involves the Breakage of Its S4 Helix.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_9F3F3B036C88
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Voltage-Dependent Deactivation of the KvAP Channel Involves the Breakage of Its S4 Helix.
Journal
Frontiers in molecular biosciences
Author(s)
Bignucolo O., Bernèche S.
ISSN
2296-889X (Print)
ISSN-L
2296-889X
Publication state
Published
Issued date
2020
Peer-reviewed
Oui
Volume
7
Pages
162
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Voltage-gated potassium channels (Kv) allow ion permeation upon changes of the membrane electrostatic potential (Vm). Each subunit of these tetrameric channels is composed of six transmembrane helices, of which the anti-parallel helix bundle S1-S4 constitutes the voltage-sensor domain (VSD) and S5-S6 forms the pore domain. Here, using 82 molecular dynamics (MD) simulations involving 266 replicated VSDs, we report novel responses of the archaebacterial potassium channel KvAP to membrane polarization. We show that the S4 α-helix, which is straight in the experimental crystal structure solved under depolarized conditions (Vm ∼ 0), breaks into two segments when the cell membrane is hyperpolarized (Vm << 0), and reversibly forms a single straight helix following depolarization (Vm = 0). The outermost segment of S4 translates along the normal to the membrane, bringing new perspective to previously paradoxical accessibility experiments that were initially thought to imply the displacement of the whole VSD across the membrane. The novel model is applied through steered and unbiased MD simulations to the recently solved whole structure of KvAP. The simulations show that the resting state involves a re-orientation of the S5 α-helix by ∼ 5-6 degrees in respect to the normal of the bilayer, which could result in the constriction and closure of the selectivity filter. Our findings support the idea that the breakage of S4 under (hyper)polarization is a general feature of Kv channels with a non-swapped topology.
Keywords
Biochemistry, Genetics and Molecular Biology (miscellaneous), Molecular Biology, Biochemistry, Kv channel, avidin accessibility, molecular dynamics, pore domain, resting state, voltage-sensor domain
Pubmed
Web of science
Open Access
Yes
Create date
03/08/2020 11:46
Last modification date
28/03/2023 5:52
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