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Molecular structures of the human Slo1 K+ channel in complex with ?4.

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, ?4. Four ?4, each containing two transmembrane helices, encircle Slo1, contacting it through helical interactions inside the membrane. On the extracellular side, ?4 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 ?4, implying that ?4 serves to modulate the relative stabilities of 'pre-existing' conformations rather than creating new ones. The effects of ?4 on scorpion toxin inhibition kinetics are explained by the crown, which constrains access but does not prevent binding.

SUBMITTER: Tao X

PROVIDER: S-EPMC6934384 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Tao Xiao X MacKinnon Roderick R

eLife 20191209

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 interactio ...[more]

PMID: 31815672

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