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Cryo-EM structure of Ca2+-bound hsSlo1-beta4 channel complexCryo-EM structure of Ca2+-bound hsSlo1-beta4 channel complex
Structural highlights
Function[KCMB4_HUMAN] Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Decreases the gating kinetics and calcium sensitivity of the KCNMA1 channel, but with fast deactivation kinetics. May decrease KCNMA1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. Makes KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin concentrations.[1] [2] [3] Publication Abstract from PubMedSlo1 is a Ca(2+)- and voltage-activated K(+) channel that underlies skeletal and smooth muscle contraction, audition, hormone secretion and neurotransmitter release. In mammals, Slo1 is regulated by auxiliary proteins that confer tissue-specific gating and pharmacological properties. This study presents cryo-EM structures of Slo1 in complex with the auxiliary protein, beta4. Four beta4, each containing two transmembrane helices, encircle Slo1, contacting it through helical interactions inside the membrane. On the extracellular side, b4 forms a tetrameric crown over the pore. Structures with high and low Ca(2+) concentrations show that identical gating conformations occur in the absence and presence of beta4, implying that beta4 serves to modulate the relative stabilities of 'pre-existing' conformations rather than creating new ones. The effects of beta4 on scorpion toxin inhibition kinetics are explained by the crown, which constrains access but does not prevent binding. Molecular structures of the human Slo1 K(+) channel in complex with beta4.,Tao X, MacKinnon R Elife. 2019 Dec 9;8. pii: 51409. doi: 10.7554/eLife.51409. PMID:31815672[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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