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

Authors :
Xiao Tao
Roderick MacKinnon
Source :
eLife, Vol 8 (2019)
Publication Year :
2019
Publisher :
eLife Sciences Publications Ltd, 2019.

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, β4 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.

Details

Language :
English
ISSN :
2050084X
Volume :
8
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.4ad26397faf64b9ba00cd134e10ad719
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.51409