ArticleThe Journal of biological chemistry2011
KCNQ1 channels voltage dependence through a voltage-dependent binding of the S4-S5 linker to the pore domain.
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 35 papers.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- Article
- Disruption of a Conservative Motif in the C-Terminal Loop of the KCNQ1 Channel Causes LQT Syndrome.International journal of molecular sciences · 2022Article
- Editorial: Molecular Mechanisms of Voltage-Gating in Ion Channels.Frontiers in pharmacology · 2021Article
- Up-regulation of voltage-gated sodium channels by peptides mimicking S4-S5 linkers reveals a variation of the ligand-receptor mechanism.Scientific reports · 2020Article
- Two-stage electro-mechanical coupling of a KNature communications · 2020Article
- Gating and Regulation of KCNQ1 and KCNQ1 + KCNE1 Channel Complexes.Frontiers in physiology · 2020Review
- The EAG Voltage-Dependent KFrontiers in pharmacology · 2020Review
- Voltage-dependent activation in EAG channels follows a ligand-receptor rather than a mechanical-lever mechanism.The Journal of biological chemistry · 2019Article
- New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question.International journal of molecular sciences · 2019Review
- 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
- 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
- PIP₂-dependent coupling is prominent in Kv7.1 due to weakened interactions between S4-S5 and S6.Scientific reports · 2015Article
- Cellular mechanisms of mutations in Kv7.1: auditory functions in Jervell and Lange-Nielsen syndrome vs. Romano-Ward syndrome.Frontiers in cellular neuroscience · 2015Article
- Purification and structural study of the voltage-sensor domain of the human KCNQ1 potassium ion channel.Biochemistry · 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
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Voltage-dependent potassium (Kv) channels are tetramers of six transmembrane domain (S1-S6) proteins. Crystallographic data demonstrate that the tetrameric pore (S5-S6) is surrounded by four voltage sensor domains (S1-S4). One key question remains: how do voltage sensors (S4) regulate pore gating? Previous mutagenesis data obtained on the Kv channel KCNQ1 highlighted the critical role of specific residues in both the S4-S5 linker (S4S5(L)) and S6 C terminus (S6(T)). From these data, we hypothesized that S4S5(L) behaves like a ligand specifically interacting with S6(T) and stabilizing the closed state. To test this hypothesis, we designed plasmid-encoded peptides corresponding to portions of S4S5(L) and S6(T) of the voltage-gated potassium channel KCNQ1 and evaluated their effects on the channel activity in the presence and absence of the ancillary subunit KCNE1. We showed that S4S5(L) peptides inhibit KCNQ1, in a reversible and state-dependent manner. S4S5(L) peptides also inhibited a voltage-independent KCNQ1 mutant. This inhibition was competitively prevented by a peptide mimicking S6(T), consistent with S4S5(L) binding to S6(T). Val(254) in S4S5(L) is known to contact Leu(353) in S6(T) when the channel is closed, and mutations of these residues alter the coupling between the two regions. The same mutations introduced in peptides altered their effects, further confirming S4S5(L) binding to S6(T). Our results suggest a mechanistic model in which S4S5(L) acts as a voltage-dependent ligand bound to its receptor on S6 at rest. This interaction locks the channel in a closed state. Upon plasma membrane depolarization, S4 pulls S4S5(L) away from S6(T), allowing channel opening.
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