ArticleThe Journal of membrane biology2005
Interactions between charged residues in the transmembrane segments of the voltage-sensing domain in the hERG channel.
Article in The Journal of membrane biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- Integrating AI and Molecular Modeling for Structural Prediction of a Closed-Pore State of the hERG Channel.Journal of chemical information and modeling · 2026Article
- Bdelloid rotifers harbor a voltage-gated proton channel with distinct mechanistic features.Nature communications · 2026Article
- Rare pathogenic mutation ofFrontiers in cardiovascular medicine · 2026Article
- Molecular Determinants of Voltage-Dependent Gating in Kv11.1 Channels.Advances in experimental medicine and biology · 2026Review
- Voltage sensor conformations induced by LQTS-associated mutations in hERG potassium channels.Nature communications · 2025Article
- An LQT2-related mutation in the voltage-sensing domain is involved in switching the gating polarity of hERG.BMC biology · 2024Article
- Modeling long QT syndrome type 2 on-a-chip via in-depth assessment of isogenic gene-edited 3D cardiac tissues.Science advances · 2022Article
- The voltage-sensing domain of a hERG1 mutant is a cation-selective channel.Biophysical journal · 2022Article
- The role of Phe150 in human voltage-gated proton channel.iScience · 2022Article
- Molecular dynamics simulations suggest possible activation and deactivation pathways in the hERG channel.Communications biology · 2022Article
- Refinement of a cryo-EM structure of hERG: Bridging structure and function.Biophysical journal · 2021Article
- Modulation of hERG KFrontiers in pharmacology · 2020Review
- The EAG Voltage-Dependent KFrontiers in pharmacology · 2020Review
- Roles for Countercharge in the Voltage Sensor Domain of Ion Channels.Frontiers in pharmacology · 2020Review
- Extracellular protons accelerate hERG channel deactivation by destabilizing voltage sensor relaxation.The Journal of general physiology · 2019Article
- The Fast Component of hERG Gating Charge: An Interaction between D411 in the S1 and S4 Residues.Biophysical journal · 2017Article
- Molecular Basis of Altered hERG1 Channel Gating Induced by Ginsenoside Rg3.Molecular pharmacology · 2017Article
- The S1 helix critically regulates the finely tuned gating of Kv11.1 channels.The Journal of biological chemistry · 2017Article
- Molecular Simulations of Solved Co-crystallized X-Ray Structures Identify Action Mechanisms of PDEδ Inhibitors.Biophysical journal · 2015Article
- Free-energy landscape of ion-channel voltage-sensor-domain activation.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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Authors and funding
7 authors.
Funding
Abstract
Studies on voltage-gated K channels such as Shaker have shown that positive charges in the voltage-sensor (S4) can form salt bridges with negative charges in the surrounding transmembrane segments in a state-dependent manner, and different charge pairings can stabilize the channels in closed or open states. The goal of this study is to identify such charge interactions in the hERG channel. This knowledge can provide constraints on the spatial relationship among transmembrane segments in the channel's voltage-sensing domain, which are necessary for modeling its structure. We first study the effects of reversing S4's positive charges on channel activation. Reversing positive charges at the outer (K525D) and inner (K538D) ends of S4 markedly accelerates hERG activation, whereas reversing the 4 positive charges in between either has no effect or slows activation. We then use the 'mutant cycle analysis' to test whether D456 (outer end of S2) and D411 (inner end of S1) can pair with K525 and K538, respectively. Other positive charges predicted to be able, or unable, to interact with D456 or D411 are also included in the analysis. The results are consistent with predictions based on the distribution of these charged residues, and confirm that there is functional coupling between D456 and K525 and between D411 and K538.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.