PDF(Pubmed)
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.
摘要：
Slo1是一种Ca2+和电压激活的K+通道，是骨骼肌和平滑肌收缩的基础，试镜,激素分泌和神经递质释放。在哺乳动物中,Slo1受赋予组织特异性门控和药理学性质的辅助蛋白调节。这项研究提出了Slo1与辅助蛋白复合的冷冻EM结构，β4.四个β4，每个包含两个跨膜螺旋，环绕Slo1，通过膜内的螺旋相互作用与之接触。在细胞外侧，β4在孔上形成四聚体冠。具有高和低Ca2浓度的结构表明，在不存在和存在β4的情况下，会发生相同的门控构象，这意味着β4可以调节\'预先存在的\'构象的相对稳定性，而不是产生新的构象。β4对蝎毒抑制动力学的影响由冠解释，它限制访问，但不阻止绑定。
