Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou, 310024, Zhejiang Province, China.
Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou, 310024, Zhejiang Province, China.
Nat Commun. 2022 Jul 8;13(1):3957. doi: 10.1038/s41467-022-31602-y.
Sodium-Potassium Pump (Na/K-ATPase, NKA) is an ion pump that generates an electrochemical gradient of sodium and potassium ions across the plasma membrane by hydrolyzing ATP. During each Post-Albers cycle, NKA exchanges three cytoplasmic sodium ions for two extracellular potassium ions through alternating changes between the E1 and E2 states. Hitherto, several steps remained unknown during the complete working cycle of NKA. Here, we report cryo-electron microscopy (cryo-EM) structures of recombinant human NKA (hNKA) in three distinct states at 2.7-3.2 Å resolution, representing the E1·3Na and E1·3Na·ATP states with cytosolic gates open and the basic E2·[2K] state, respectively. This work provides the insights into the cytoplasmic Na entrance pathway and the mechanism of cytoplasmic gate closure coupled with ATP hydrolysis, filling crucial gaps in the structural elucidation of the Post-Albers cycle of NKA.
钠钾泵（Na/K-ATPase，NKA）是一种离子泵，通过水解 ATP 在质膜两侧产生钠离子和钾离子的电化学梯度。在每个阿尔伯斯后循环中，NKA 通过 E1 和 E2 状态的交替变化，将三个细胞质钠离子交换为两个细胞外钾离子。迄今为止，在 NKA 的完整工作循环中，仍有几个步骤尚不清楚。在这里，我们报道了 2.7-3.2Å 分辨率下三种不同状态的重组人 NKA（hNKA）的冷冻电镜（cryo-EM）结构，分别代表细胞质门打开的 E1·3Na 和 E1·3Na·ATP 状态，以及基本的 E2·[2K]状态。这项工作深入了解了细胞质 Na 入口途径和与 ATP 水解偶联的细胞质门关闭机制，填补了 NKA 阿尔伯斯后循环结构阐明中的关键空白。
