ArticleBiophysical journal2010
Mutations within the S4-S5 linker alter voltage sensor constraints in hERG K+ channels.
Article in Biophysical journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- An LQT2-related mutation in the voltage-sensing domain is involved in switching the gating polarity of hERG.BMC biology · 2024Article
- The voltage-sensing domain of a hERG1 mutant is a cation-selective channel.Biophysical journal · 2022Article
- Refinement of a cryo-EM structure of hERG: Bridging structure and function.Biophysical journal · 2021Article
- Modulation of hERG KFrontiers in pharmacology · 2020Review
- Extracellular protons accelerate hERG channel deactivation by destabilizing voltage sensor relaxation.The Journal of general physiology · 2019Article
- Gating mechanism of Kv11.1 (hERG) KPflugers Archiv : European journal of physiology · 2018Article
- The Fast Component of hERG Gating Charge: An Interaction between D411 in the S1 and S4 Residues.Biophysical journal · 2017Article
- A new mechanism of voltage-dependent gating exposed by KThe Journal of general physiology · 2017Article
- Stabilization of the Activated hERG Channel Voltage Sensor by Depolarization Involves the S4-S5 Linker.Biophysical journal · 2017Article
- Tyrosine Residues from the S4-S5 Linker of Kv11.1 Channels Are Critical for Slow Deactivation.The Journal of biological chemistry · 2016Article
- Getting to the heart of hERG K(+) channel gating.The Journal of physiology · 2015Review
- Voltage-dependent gating of KCNH potassium channels lacking a covalent link between voltage-sensing and pore domains.Nature communications · 2015Article
- NS1643 interacts around L529 of hERG to alter voltage sensor movement on the path to activation.Biophysical journal · 2015Article
- Sequence of gating charge movement and pore gating in HERG activation and deactivation pathways.Biophysical journal · 2015Article
- Regional flexibility in the S4-S5 linker regulates hERG channel closed-state stabilization.Pflugers Archiv : European journal of physiology · 2014Article
- Proline scan of the HERG channel S6 helix reveals the location of the intracellular pore gate.Biophysical journal · 2014Article
- External protons destabilize the activated voltage sensor in hERG channels.European biophysics journal : EBJ · 2014Article
- Article
- Components of gating charge movement and S4 voltage-sensor exposure during activation of hERG channels.The Journal of general physiology · 2013Article
- Perspectives on: conformational coupling in ion channels: thermodynamics of electromechanical coupling in voltage-gated ion channels.The Journal of general physiology · 2012Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human ether-a-go-go related gene (hERG) channel gating is associated with slow activation, yet the mechanistic basis for this is unclear. Here, we examine the effects of mutation of a unique glycine residue (G546) in the S4-S5 linker on voltage sensor movement and its coupling to pore gating. Substitution of G546 with residues possessing different physicochemical properties shifted activation gating by ∼-50 mV (with the exception of G546C). With the activation shift taken into account, the time constant of activation was also accelerated, suggesting a stabilization of the closed state by ∼1.6-4.3 kcal/mol (the energy equivalent of one to two hydrogen bonds). Predictions of the α-helical content of the S4-S5 linker suggest that the presence of G546 in wild-type hERG provides flexibility to the helix. Deactivation gating was affected differentially by the G546 substitutions. G546V induced a pronounced slow component of closing that was voltage-independent. Fluorescence measurements of voltage sensor movement in G546V revealed a slow component of voltage sensor return that was uncoupled from charge movement, suggesting a direct effect of the mutation on voltage sensor movement. These data suggest that G546 plays a critical role in channel gating and that hERG channel closing involves at least two independently modifiable reconfigurations of the voltage sensor.
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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.