ArticleThe EMBO journal2008
Structural determinants of Kvbeta1.3-induced channel inactivation: a hairpin modulated by PIP2.
Article in The EMBO journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Lipid trapping slows ball-and-chain inactivation in a calcium-activated potassium channel.Nature communications · 2026Article
- Lgi3-4 proteins modulate the KV1.5 channelosome and are potential therapeutic targets for atrial fibrillation.Cardiovascular research · 2026Article
- Voltage-dependent potassium channel regulatory subunits in the immune system.Biophysical reviews · 2026Review
- PIPProceedings of the National Academy of Sciences of the United States of America · 2020Review
- KChannels (Austin, Tex.) · 2018Article
- Transmural gradients in ion channel and auxiliary subunit expression.Progress in biophysics and molecular biology · 2016Review
- Human EAG channels are directly modulated by PIP2 as revealed by electrophysiological and optical interference investigations.Scientific reports · 2016Article
- Ca(2+)/calmodulin regulates Kvβ1.1-mediated inactivation of voltage-gated K(+) channels.Scientific reports · 2015Article
- Transient receptor potential melastatin 3 is a phosphoinositide-dependent ion channel.The Journal of general physiology · 2015Article
- Phosphoinositides regulate ion channels.Biochimica et biophysica acta · 2015Review
- Cortisone and hydrocortisone inhibit human Kv1.3 activity in a non-genomic manner.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Phosphoinositide control of membrane protein function: a frontier led by studies on ion channels.Annual review of physiology · 2015Review
- Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2 channel gating.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Side pockets provide the basis for a new mechanism of Kv channel-specific inhibition.Nature chemical biology · 2013Article
- Conserved N-terminal negative charges support optimally efficient N-type inactivation of Kv1 channels.PloS one · 2013Article
- Regulation of voltage-gated potassium channels by PI(4,5)P2.The Journal of general physiology · 2012Article
- Protein kinase C (PKC) activity regulates functional effects of Kvβ1.3 subunit on KV1.5 channels: identification of a cardiac Kv1.5 channelosome.The Journal of biological chemistry · 2012Article
- Dual Regulation of Voltage-Sensitive Ion Channels by PIP(2).Frontiers in pharmacology · 2012Article
- Polyunsaturated Fatty acids modify the gating of kv channels.Frontiers in pharmacology · 2012Article
- Oxidation of NADPH on Kvbeta1 inhibits ball-and-chain type inactivation by restraining the chain.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Inactivation of voltage-gated Kv1 channels can be altered by Kvbeta subunits, which block the ion-conducting pore to induce a rapid ('N-type') inactivation. Here, we investigate the mechanisms and structural basis of Kvbeta1.3 interaction with the pore domain of Kv1.5 channels. Inactivation induced by Kvbeta1.3 was antagonized by intracellular PIP(2). Mutations of R5 or T6 in Kvbeta1.3 enhanced Kv1.5 inactivation and markedly reduced the effects of PIP(2). R5C or T6C Kvbeta1.3 also exhibited diminished binding of PIP(2) compared with wild-type channels in an in vitro lipid-binding assay. Further, scanning mutagenesis of the N terminus of Kvbeta1.3 revealed that mutations of L2 and A3 eliminated N-type inactivation. Double-mutant cycle analysis indicates that R5 interacts with A501 and T480 of Kv1.5, residues located deep within the pore of the channel. These interactions indicate that Kvbeta1.3, in contrast to Kvbeta1.1, assumes a hairpin structure to inactivate Kv1 channels. Taken together, our findings indicate that inactivation of Kv1.5 is mediated by an equilibrium binding of the N terminus of Kvbeta1.3 between phosphoinositides (PIPs) and the inner pore region of the channel.
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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.