ArticleThe Journal of biological chemistry2008
Structural basis for toxin resistance of beta4-associated calcium-activated potassium (BK) channels.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications.International journal of molecular sciences · 2024Review
- Large conductance voltage-and calcium-activated KFrontiers in pharmacology · 2024Review
- CaInternational journal of molecular sciences · 2023Review
- Development of charybdotoxin Q18F variant as a selective peptide blocker of neuronal BK(α + β4) channel for the treatment of epileptic seizures.Protein science : a publication of the Protein Society · 2022Article
- Homology modeling and molecular docking simulation of martentoxin as a specific inhibitor of the BK channel.Annals of translational medicine · 2022Article
- Glycosylation of β1 subunit plays a pivotal role in the toxin sensitivity and activation of BK channels.The journal of venomous animals and toxins including tropical diseases · 2021Article
- Control of Biophysical and Pharmacological Properties of Potassium Channels by Ancillary Subunits.Handbook of experimental pharmacology · 2021Article
- Calcium-induced calcium release in proximity to hair cell BK channels revealed by PKA activation.Physiological reports · 2020Article
- Article
- Diverse Structural Features of Potassium Channels Characterized by Scorpion Toxins as Molecular Probes.Molecules (Basel, Switzerland) · 2019Review
- Solution structure of extracellular loop of human β4 subunit of BK channel and its biological implication on ChTX sensitivity.Scientific reports · 2018Article
- Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations.Science signaling · 2016Article
- Scorpion Potassium Channel-blocking Defensin Highlights a Functional Link with Neurotoxin.The Journal of biological chemistry · 2016Article
- Modulation of BK Channel Function by Auxiliary Beta and Gamma Subunits.International review of neurobiology · 2016Review
- A single conserved basic residue in the potassium channel filter region controls KCNQ1 insensitivity toward scorpion toxins.Biochemistry and biophysics reports · 2015Article
- Article
- Binding modes of two scorpion toxins to the voltage-gated potassium channel kv1.3 revealed from molecular dynamics.Toxins · 2014Article
- Review
- Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits.Frontiers in physiology · 2014Review
- Current understanding of iberiotoxin-resistant BK channels in the nervous system.Frontiers in physiology · 2014Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The functional diversity of large conductance Ca(2+)- and voltage-dependent K(+) (BK) channels arises mainly from co-assembly of the pore-forming mSlo alpha subunits with four tissue-enriched auxiliary beta subunits. The structural basis of the interaction between alpha subunits with beta subunits is not well understood. Using computational and experimental methods, we demonstrated that four mSlo turrets decentralized distally from the channel pore to provide a wide open conformation and that the mSlo and hbeta4 subunits together formed a "helmet" containing three basic residues (Lys-120, Arg-121, and Lys-125), which impeded the entry of charybdotoxin (ChTX) by both the electrostatic interaction and limited space. In addition, the tyrosine insert mutant (in100Y) showed 56% inhibition, with a K(d) = 17 nm, suggesting that the hbeta4 lacks an external ChTX-binding site (Tyr-100). We also found that mSlo had an internal binding site (Tyr-294) in the alpha subunits that could "permanently" block 15% of mSlo+hbeta4 currents in the presence of 100 nm ChTX. These findings provide a better understanding of the diverse interactions between alpha and beta subunits and will improve the design of channel inhibitors.
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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.