ArticleThe Journal of biological chemistry2014
Multiple interactions between cytoplasmic domains regulate slow deactivation of Kv11.1 channels.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- An intracellular hydrophobic nexus critical for hERG1 channel slow deactivation.Biophysical journal · 2024Article
- Article
- Development of automated patch clamp assays to overcome the burden of variants of uncertain significance in inheritable arrhythmia syndromes.Frontiers in physiology · 2023Review
- Binding of RPR260243 at the intracellular side of the hERG1 channel pore domain slows closure of the helix bundle crossing gate.Frontiers in molecular biosciences · 2023Article
- A massively parallel assay accurately discriminates between functionally normal and abnormal variants in a hotspot domain of KCNH2.American journal of human genetics · 2022Article
- Hysteretic hERG channel gating current recorded at physiological temperature.Scientific reports · 2022Article
- Conformation-sensitive antibody reveals an altered cytosolic PAS/CNBh assembly during hERG channel gating.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Electrophysiological characterization of the hERG R56Q LQTS variant and targeted rescue by the activator RPR260243.The Journal of general physiology · 2021Article
- hERG Function in Light of Structure.Biophysical journal · 2020Review
- Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome.Frontiers in pharmacology · 2020Review
- The EAG Voltage-Dependent KFrontiers in pharmacology · 2020Review
- The hERG potassium channel intrinsic ligand regulates N- and C-terminal interactions and channel closure.The Journal of general physiology · 2019Article
- Extracellular protons accelerate hERG channel deactivation by destabilizing voltage sensor relaxation.The Journal of general physiology · 2019Article
- Two mutations at different positions in the CNBH domain of the hERG channel accelerate deactivation and impair the interaction with the EAG domain.The Journal of physiology · 2018Article
- Never at rest: insights into the conformational dynamics of ion channels from cryo-electron microscopy.The Journal of physiology · 2018Review
- Determinants of Isoform-Specific Gating Kinetics of hERG1 Channel: Combined Experimental and Simulation Study.Frontiers in physiology · 2018Article
- Development of a High-Throughput Flow Cytometry Assay to Monitor Defective Trafficking and Rescue of Long QT2 Mutant hERG Channels.Frontiers in physiology · 2018Article
- Towards a Structural View of Drug Binding to hERG KTrends in pharmacological sciences · 2017Review
- The S1 helix critically regulates the finely tuned gating of Kv11.1 channels.The Journal of biological chemistry · 2017Article
- The intrinsically liganded cyclic nucleotide-binding homology domain promotes KCNH channel activation.The Journal of general physiology · 2017Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intracellular domains of many ion channels are important for fine-tuning their gating kinetics. In Kv11.1 channels, the slow kinetics of channel deactivation, which are critical for their function in the heart, are largely regulated by the N-terminal N-Cap and Per-Arnt-Sim (PAS) domains, as well as the C-terminal cyclic nucleotide-binding homology (cNBH) domain. Here, we use mutant cycle analysis to probe for functional interactions between the N-Cap/PAS domains and the cNBH domain. We identified a specific and stable charge-charge interaction between Arg(56) of the PAS domain and Asp(803) of the cNBH domain, as well an additional interaction between the cNBH domain and the N-Cap, both of which are critical for maintaining slow deactivation kinetics. Furthermore, we found that positively charged arginine residues within the disordered region of the N-Cap interact with negatively charged residues of the C-linker domain. Although this interaction is likely more transient than the PAS-cNBD interaction, it is strong enough to stabilize the open conformation of the channel and thus slow deactivation. These findings provide novel insights into the slow deactivation mechanism of Kv11.1 channels.
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