Cryo-EM structures of recombinant human sodium-potassium pump determined in three different states.

Cryo-EM structures of recombinant human sodium-potassium pump determined in three different states.
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DOI:
10.1038/s41467-022-31602-y
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发表时间:
2022-07-08
影响因子:
16.6
通讯作者:
Zhou, Qiang
Zhou, Qiang
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Guo, Yingying;Zhang, Yuanyuan;Yan, Renhong;Huang, Bangdong;Ye, Fangfei;Wu, Liushu;Chi, Ximin;Shi, Yi;Zhou, Qiang

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钠钾泵(Na+/K+-ATP酶,NKA)是一种离子泵,通过水解ATP在质膜上产生钠离子和钾离子的电化学梯度。在每个Post-Albers周期中,NKA通过E1和E2状态的交替变化将3个胞质钠离子交换为2个胞外钾离子。迄今为止,在NKA的整个工作周期中,有几个步骤仍然未知。在这里,我们报道了重组人NKA (hNKA)在2.7-3.2 Å分辨率下三种不同状态下的冷冻电镜(cro - em)结构,分别代表E1·3Na和E1·3Na·ATP状态,细胞质门打开,碱性E2·[2K]状态。这项工作提供了细胞质Na+入口途径和细胞质门关闭与ATP水解耦合的机制的见解,填补了NKA后albers循环结构阐明的关键空白。钠钾泵(Na+/K+-ATP酶,NKA)通过水解ATP在质膜上产生钠离子和钾离子的电化学梯度。在这里,作者报告了人类NKA的结构,提供了细胞质Na+入口和细胞质门关闭耦合到ATP水解的见解。
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. Sodium-Potassium Pump (Na+/K+-ATPase, NKA) generates an electrochemical gradient of sodium and potassium ions across the plasma membrane by hydrolyzing ATP. Here, the authors report structures of human NKA providing insight into the cytoplasmic Na+ entrance and the cytoplasmic gate closure coupled to ATP hydrolysis.
DOI: 10.1038/s41467-021-26024-1
发表时间: 2021-09-29
影响因子: 16.6
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期刊: ULTRAMICROSCOPY
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