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Molecular structures of the human Slo1 K(+) channel in complex with β4

Slo1 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 pres...

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Detalles Bibliográficos
Autores principales: Tao, Xiao, MacKinnon, Roderick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934384/
https://www.ncbi.nlm.nih.gov/pubmed/31815672
http://dx.doi.org/10.7554/eLife.51409
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author Tao, Xiao
MacKinnon, Roderick
author_facet Tao, Xiao
MacKinnon, Roderick
author_sort Tao, Xiao
collection PubMed
description Slo1 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, β4. Four β4, each containing two transmembrane helices, encircle Slo1, contacting it through helical interactions inside the membrane. On the extracellular side, β4 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 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.
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spelling pubmed-69343842019-12-30 Molecular structures of the human Slo1 K(+) channel in complex with β4 Tao, Xiao MacKinnon, Roderick eLife Structural Biology and Molecular Biophysics Slo1 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, β4. Four β4, each containing two transmembrane helices, encircle Slo1, contacting it through helical interactions inside the membrane. On the extracellular side, β4 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 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. eLife Sciences Publications, Ltd 2019-12-09 /pmc/articles/PMC6934384/ /pubmed/31815672 http://dx.doi.org/10.7554/eLife.51409 Text en © 2019, Tao and MacKinnon http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Structural Biology and Molecular Biophysics
Tao, Xiao
MacKinnon, Roderick
Molecular structures of the human Slo1 K(+) channel in complex with β4
title Molecular structures of the human Slo1 K(+) channel in complex with β4
title_full Molecular structures of the human Slo1 K(+) channel in complex with β4
title_fullStr Molecular structures of the human Slo1 K(+) channel in complex with β4
title_full_unstemmed Molecular structures of the human Slo1 K(+) channel in complex with β4
title_short Molecular structures of the human Slo1 K(+) channel in complex with β4
title_sort molecular structures of the human slo1 k(+) channel in complex with β4
topic Structural Biology and Molecular Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934384/
https://www.ncbi.nlm.nih.gov/pubmed/31815672
http://dx.doi.org/10.7554/eLife.51409
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