The beryllium fluoride form of the Na + ,K + -ATPase and the intermediates of the functional cycle
The beryllium fluoride form of the Na + ,K + -ATPase and the intermediates of the functional cycle
Abstract The Na+,K+-ATPase generates electrochemical gradients of Na+ and K+ across the plasma membrane. Here, we describe a 4.0 ? resolution crystal structure of the pig kidney Na+,K+-ATPase stabilized by beryllium fluoride (denoted E2-BeFx). The structure shows high resemblance to the E2P phosphoenzyme obtained by phosphorylation from inorganic phosphate (Pi) and stabilised by cardiotonic steroids, and reveals a Mg2+ bound near the ion binding site II. Anomalous Fourier analysis of the crystals soaked in Rb+ (K+ congener) followed by a low resolution rigid-body refinement (6.9-7.5 ?) revealed pre-occlusion transitions leading to activation of the desphosphorylation reaction. Mg2+ location indicates a site of an initial K+ recognition and acceptance upon binding to the outward-open E2P state after Na+ release. Despite the overall structural resemblance to the Pi-induced E2P phosphoform, BeFx inhibited enzyme is able to bind both ADP/ATP and ions - features that relate E2-BeFx complex to an intermediate of the functional cycle of the Na+,K+-ATPase prior E2P.
Quistgaard Esben M.、Nissen Poul、Fruergaard Marlene U.、Poulsen Hanne、Dach Ingrid、Shasavar Azadeh、Ozol Mette、Fedosova Natalya U.、Andersen Jacob L.
DANDRITE - Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Dept. Molecular Biology and GeneticsDANDRITE - Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Dept. Molecular Biology and GeneticsDANDRITE - Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Dept. Molecular Biology and GeneticsDANDRITE - Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Dept. Molecular Biology and GeneticsDANDRITE - Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Dept. Molecular Biology and GeneticsDANDRITE - Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Dept. Molecular Biology and GeneticsDANDRITE - Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Dept. Molecular Biology and GeneticsDepartment of Biomedicine, Aarhus UniversityDANDRITE - Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Dept. Molecular Biology and Genetics||Department of Biomedicine, Aarhus University
生物化学生物物理学生理学
Quistgaard Esben M.,Nissen Poul,Fruergaard Marlene U.,Poulsen Hanne,Dach Ingrid,Shasavar Azadeh,Ozol Mette,Fedosova Natalya U.,Andersen Jacob L..The beryllium fluoride form of the Na + ,K + -ATPase and the intermediates of the functional cycle[EB/OL].(2025-03-28)[2025-04-30].https://www.biorxiv.org/content/10.1101/2021.11.08.467847.点此复制
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