ArticleThe Journal of biological chemistry2012
Multiple cholesterol recognition/interaction amino acid consensus (CRAC) motifs in cytosolic C tail of Slo1 subunit determine cholesterol sensitivity of Ca2+- and voltage-gated K+ (BK) channels.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 106 citations in OpenAlex.
- Site and mechanism of BK channel inhibition and cerebral artery constriction by pregnenolone.Pharmacological research · 2026Article
- Molecular determinants of cholesterol binding to BK channel-forming slo1 subunits.Archives of biochemistry and biophysics · 2026Article
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Cholesterol, PtdIns(4,5)PbioRxiv : the preprint server for biology · 2026Article
- Article
- Cholesterol and docosahexaenoic acid likely protect against alcohol-induced constriction of cerebral arteries via a common pathway.Advances in drug and alcohol research · 2026Article
- Physics-based evolution of transmembrane helices reveals mechanisms of cholesterol attraction.Nature communications · 2025Article
- Shear Stress Regulates ABCA1-Dependent Membrane Cholesterol Content in Endothelial Cells Facilitating HMicrocirculation (New York, N.Y. : 1994) · 2025Article
- Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis.PLoS pathogens · 2025Article
- The Slo1 Y450F Substitution Modifies Basal Function and Cholesterol Response of Middle Cerebral Artery Smooth Muscle BK Channels in a Sexually Dimorphic Manner.International journal of molecular sciences · 2025Article
- Subunit-specific inhibition of BK channels by piperine.Biophysical journal · 2024Article
- Progesterone activation of βNature communications · 2023Article
- Differential Functional Contribution of BK Channel Subunits to Aldosterone-Induced Channel Activation in Vascular Smooth Muscle and Eventual Cerebral Artery Dilation.International journal of molecular sciences · 2023Article
- Cholesterol and PIPAdvances in experimental medicine and biology · 2023Article
- PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Endothelial cell membrane cholesterol content regulates the contribution of TRPV4 channels in ACh-induced vasodilation in rat gracilis arteries.Microcirculation (New York, N.Y. : 1994) · 2022Article
- Cholesterol-induced suppression of Kir2 channels is mediated by decoupling at the inter-subunit interfaces.iScience · 2022Article
- A molecular switch controls the impact of cholesterol on a Kir channel.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cholesterol Inhibition of Slo1 Channels Is Calcium-Dependent and Can Be Mediated by Either High-Affinity Calcium-Sensing Site in the Slo1 Cytosolic Tail.Molecular pharmacology · 2022Article
- Mitochondrial potassium channels: A novel calcitriol target.Cellular & molecular biology letters · 2022Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Large conductance, Ca(2+)- and voltage-gated K(+) (BK) channel proteins are ubiquitously expressed in cell membranes and control a wide variety of biological processes. Membrane cholesterol regulates the activity of membrane-associated proteins, including BK channels. Cholesterol modulation of BK channels alters action potential firing, colonic ion transport, smooth muscle contractility, endothelial function, and the channel alcohol response. The structural bases underlying cholesterol-BK channel interaction are unknown. Such interaction is determined by strict chemical requirements for the sterol molecule, suggesting cholesterol recognition by a protein surface. Here, we demonstrate that cholesterol action on BK channel-forming Cbv1 proteins is mediated by their cytosolic C tail domain, where we identified seven cholesterol recognition/interaction amino acid consensus motifs (CRAC4 to 10), a distinct feature of BK proteins. Cholesterol sensitivity is provided by the membrane-adjacent CRAC4, where Val-444, Tyr-450, and Lys-453 are required for cholesterol sensing, with hydrogen bonding and hydrophobic interactions participating in cholesterol location and recognition. However, cumulative truncations or Tyr-to-Phe substitutions in CRAC5 to 10 progressively blunt cholesterol sensitivity, documenting involvement of multiple CRACs in cholesterol-BK channel interaction. In conclusion, our study provides for the first time the structural bases of BK channel cholesterol sensitivity; the presence of membrane-adjacent CRAC4 and the long cytosolic C tail domain with several other CRAC motifs, which are not found in other members of the TM6 superfamily of ion channels, very likely explains the unique cholesterol sensitivity of BK channels.
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