Open and Closed Structures of a Barium-Blocked Potassium Channel

JOURNAL OF MOLECULAR BIOLOGY

卷:432

Article

Rohaim, Ahmed^1,2  Gong, LiDong³  Li, Jing¹  Rui, Huan¹  Blachowicz, Lydia¹  Roux, Benoit¹ 

[1] Univ Chicago, Gordon Ctr Integrat Sci, Dept Biochem & Mol Biol, 929 E 57th St, Chicago, IL 60637 USA

[2] Cairo Univ, Fac Sci, Dept Biophys, Giza 12613, Egypt

[3] Liaoning Normal Univ, Sch Chem & Chem Engn, Dalian 116029, Peoples R China

关键词: crystallography;    molecular dynamics;    free energy;    binding;    polarization;   

DOI  :  10.1016/j.jmb.2020.06.012

来源: Elsevier

【 摘 要 】

Barium (Ba2+) is a classic permeant blocker of potassium (K+) channels. The external lock-in effect in barium block experiments, whereby the binding of external K+ impedes the forward translocation of the blocker, provides a powerful avenue to investigate the selectivity of the binding sites along the pore of potassium channels. Barium block experiments show that the external lock-in site is highly selective for K+ over Na+. Wild-type KcsA was crystallized in low K+ conditions, and the crystals were soaked in solutions containing various concentrations of barium. Structural analysis reveals open and closed gate conformations of the KcsA channel. Anomalous diffraction experiments show that Ba2+ primarily binds to the innermost site S4 of the selectivity filter of the open-gate conformation and also the site S2, but no binding is detected with the closedgate conformation. Alchemical free-energy perturbation calculations indicate that the presence of a Ba2+ ion in the selectivity filter boosts the specificity of K+ binding relative to Na+ in the external sites S0-S2. (C) 2020 Elsevier Ltd. All rights reserved.

【 授权许可】

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