Institute for Quantitative Biosciences, The University of Tokyo, Bunkyo-ku, Japan.
Department of Biomedicine, Aarhus University, Denmark.
FEBS Lett. 2023 Aug;597(15):1957-1976. doi: 10.1002/1873-3468.14689. Epub 2023 Jul 6.
Na ,K -ATPase (NKA) plays a pivotal role in establishing electrochemical gradients for Na and K across the cell membrane by alternating between the E1 (showing high affinity for Na and low affinity for K ) and E2 (low affinity to Na and high affinity to K ) forms. Presented here are two crystal structures of NKA in E1·Mg and E1·3Na states at 2.9 and 2.8 Å resolution, respectively. These two E1 structures fill a gap in our description of the NKA reaction cycle based on the atomic structures. We describe how NKA converts the K -bound E2·2K form to an E1 (E1·Mg ) form, which allows high-affinity Na binding, eventually closing the cytoplasmic gate (in E1 ~ P·ADP·3Na ) after binding three Na , while keeping the extracellular ion pathway sealed. We now understand previously unknown functional roles for several parts of NKA and that NKA uses even the lipid bilayer for gating the ion pathway.
钠钾泵（NKA）通过在 E1（对 Na 具有高亲和力和对 K 具有低亲和力）和 E2（对 Na 具有低亲和力和对 K 具有高亲和力）形式之间交替，在细胞膜上建立 Na 和 K 的电化学梯度方面发挥着关键作用。本文呈现了两种处于 E1·Mg 和 E1·3Na 状态的 NKA 的晶体结构，分辨率分别为 2.9 和 2.8 Å。这两个 E1 结构填补了我们基于原子结构描述 NKA 反应循环的空白。我们描述了 NKA 如何将 K 结合的 E2·2K 形式转化为 E1（E1·Mg）形式，从而允许高亲和力的 Na 结合，最终在结合三个 Na 后关闭细胞质门（在 E1·P·ADP·3Na 中），同时保持细胞外离子通道关闭。我们现在了解了 NKA 的几个部分以前未知的功能作用，并且 NKA 甚至使用脂质双层来控制离子通道的开启。
