选择性
化学
生物物理学
滤波器(信号处理)
生物
生物化学
计算机科学
计算机视觉
催化作用
作者
Young Woo Nam,Mario Tringides,Dohyun Im,Hai M. Nguyen,Yan Liu,Chih‐Chia Su,Meng Cui,Heike Wulff,Edward Yu,Miao Zhang
标识
DOI:10.1016/j.bpj.2023.11.272
摘要
Small-conductance Ca2+-activated potassium (KCa2.2, also called SK2) channels are activated exclusively by a Ca2+-calmodulin (CaM) gating mechanism. To generate structural models for the KCa2.x subfamily, we determined the structures of the KCa2.2 in complex with CaM (apo-KCa2.2/CaM) and the same complex bound with a negative gating modulator AP14145 (AP14145-KCa2.2/CaM). The cryogenic-electron microscopy (cryo-EM) structures were determined at ∼2.9 angstrom resolution in the presence of Ca2+. Unlike other K+ channels, the extracellular S3-S4 loop is well structured and protrudes over the outer pore region in apo-KCa2.2/CaM. Hydrogen bonds and a salt bridge between the S3-S4 loop, the turret, and the outer selectivity filter contribute to the conformation of the S3-S4 loop. In the apo-KCa2.2/CaM structure, the selectivity filter resembles that of a previously reported KCa3.1/CaM structure. In AP14145-KCa2.2/CaM structure, binding of AP14145 to the channel’s central cavity induces conformational changes and perturbation of K+ binding within the selectivity filter, which may underlie the inhibition of KCa2.2 channels by AP14145.
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