ArticleThe Journal of biological chemistry2011
The S4-S5 linker of KCNQ1 channels forms a structural scaffold with the S6 segment controlling gate closure.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
- Structural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277.Nature communications · 2022Article
- Up-regulation of voltage-gated sodium channels by peptides mimicking S4-S5 linkers reveals a variation of the ligand-receptor mechanism.Scientific reports · 2020Article
- Gating and Regulation of KCNQ1 and KCNQ1 + KCNE1 Channel Complexes.Frontiers in physiology · 2020Review
- Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome.Frontiers in pharmacology · 2020Review
- Epilepsy-associated mutations in the voltage sensor of KCNQ3 affect voltage dependence of channel opening.The Journal of general physiology · 2019Article
- Article
- Phosphatidylinositol 4,5-bisphosphate (PIPThe Journal of biological chemistry · 2018Article
- Effects of β-subunit on gating of a potassium ion channel: Molecular simulations of cardiac IKs activation.Journal of molecular and cellular cardiology · 2018Article
- Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance.Circulation. Cardiovascular genetics · 2017Article
- A new mechanism of voltage-dependent gating exposed by KThe Journal of general physiology · 2017Article
- Gating mechanisms underlying deactivation slowing by two KCNQ1 atrial fibrillation mutations.Scientific reports · 2017Article
- hERG S4-S5 linker acts as a voltage-dependent ligand that binds to the activation gate and locks it in a closed state.Scientific reports · 2017Article
- Molecular Pathophysiology of Congenital Long QT Syndrome.Physiological reviews · 2017Review
- Voltage-Dependent Gating: Novel Insights from KCNQ1 Channels.Biophysical journal · 2016Review
- Intra- and Intersubunit Dynamic Binding in Kv4.2 Channel Closed-State Inactivation.Biophysical journal · 2016Article
- Cellular mechanisms of mutations in Kv7.1: auditory functions in Jervell and Lange-Nielsen syndrome vs. Romano-Ward syndrome.Frontiers in cellular neuroscience · 2015Article
- Trans-activation response (TAR) RNA-binding protein 2 is a novel modulator of transient receptor potential canonical 4 (TRPC4) protein.The Journal of biological chemistry · 2014Article
- Mutation of I696 and W697 in the TRP box of vanilloid receptor subtype I modulates allosteric channel activation.The Journal of general physiology · 2014Article
- Aromatic-aromatic interactions between residues in KCa3.1 pore helix and S5 transmembrane segment control the channel gating process.The Journal of general physiology · 2014Article
- Cooperative activation of the T-type CaV3.2 channel: interaction between Domains II and III.The Journal of biological chemistry · 2013Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vivo, KCNQ1 α-subunits associate with the β-subunit KCNE1 to generate the slowly activating cardiac potassium current (I(Ks)). Structurally, they share their topology with other Kv channels and consist out of six transmembrane helices (S1-S6) with the S1-S4 segments forming the voltage-sensing domain (VSD). The opening or closure of the intracellular channel gate, which localizes at the bottom of the S6 segment, is directly controlled by the movement of the VSD via an electromechanical coupling. In other Kv channels, this electromechanical coupling is realized by an interaction between the S4-S5 linker (S4S5(L)) and the C-terminal end of S6 (S6(T)). Previously we reported that substitutions for Leu(353) in S6(T) resulted in channels that failed to close completely. Closure could be incomplete because Leu(353) itself is the pore-occluding residue of the channel gate or because of a distorted electromechanical coupling. To resolve this and to address the role of S4S5(L) in KCNQ1 channel gating, we performed an alanine/tryptophan substitution scan of S4S5(L). The residues with a "high impact" on channel gating (when mutated) clustered on one side of the S4S5(L) α-helix. Hence, this side of S4S5(L) most likely contributes to the electromechanical coupling and finds its residue counterparts in S6(T). Accordingly, substitutions for Val(254) resulted in channels that were partially constitutively open and the ability to close completely was rescued by combination with substitutions for Leu(353) in S6(T). Double mutant cycle analysis supported this cross-talk indicating that both residues come in close contact and stabilize the closed state of the channel.
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