Molecular structures of the human Slo1 K+ channel in complex with β4
- Howard Hughes Medical Institute, The Rockefeller University, United States
Abstract
Slo1 is a Ca2+- 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, β4. Four β4, 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 Ca2+ concentrations show that identical gating conformations occur in the absence and presence of β4, implying that β4 serves to modulate the relative stabilities of 'pre-existing' conformations rather than creating new ones. The effects of β4 on scorpion toxin inhibition kinetics are explained by the crown, which constrains access but does not prevent binding.
Data availability
The B-factor sharpened 3D cryo-EM density maps and atomic coordinates of the Ca2+-bound (open) hsSlo1-beta4 complex (accession number EMD-21025 and 6V22), the Ca2+-free (closed) hsSlo1-beta4 complex (accession number EMD-21028 and 6V35), the Ca2+-bound (open) hsSlo1 (accession number EMD-21029 and 6V38), and the Ca2+-free (closed) hsSlo1 (accession number EMD-21036 and 6V3G) have been deposited in the Worldwide Protein Data Bank (wwPDB).
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Single particle cryo-EM structure of Ca2+-bound (open) hsSlo1-beta4 complexProtein Data Bank, EMD-21025 and PDB 6V22.
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Single particle cryo-EM structure of Ca2+-free (closed) hsSlo1-beta4 complexProtein Data Bank, EMD-21028 and PDB 6V35.
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Single particle cryo-EM structure of Ca2+-bound (open) hsSlo1Protein Data Bank, EMD-21029 and PDB 6V38.
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Single particle cryo-EM structure of Ca2+-free (closed) hsSlo1Protein Data Bank, EMD-21036 and PDB 6V3G.
Article and author information
Author details
Roderick MacKinnon
Funding
National Institutes of Health (GM43949)
- Roderick MacKinnon
Howard Hughes Medical Institute
- Roderick MacKinnon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Tao & MacKinnon
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Molecular structures of the human Slo1 K+ channel in complex with β4
eLife 8:e51409.
https://doi.org/10.7554/eLife.51409
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