Cryo-EM structures of the human Slo1 channel in complex with the auxiliary protein β4 reveal that β4 forms a tetrameric crown over the pore and modulates pre-existing gating conformations.
Cryo-EM structures reveal that the auxiliary protein β4 modulates the human Slo1 K+ channel by stabilizing pre-existing conformations and constraining access to the pore.
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.
Tao et al. (Mon,) conducted a other in Slo1 K+ channel structure. Cryo-EM structural analysis was evaluated. Cryo-EM structures of the human Slo1 channel in complex with the auxiliary protein β4 reveal that β4 forms a tetrameric crown over the pore and modulates pre-existing gating conformations.