人类钠钾泵门控机制的结构基础。
Structural basis for gating mechanism of the human sodium-potassium pump.
机构信息
Howard Hughes Medical Institute and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
出版信息
Nat Commun. 2022 Sep 8;13(1):5293. doi: 10.1038/s41467-022-32990-x.
P2-type ATPase sodium-potassium pumps (Na/K-ATPases) are ion-transporting enzymes that use ATP to transport Na and K on opposite sides of the lipid bilayer against their electrochemical gradients to maintain ion concentration gradients across the membranes in all animal cells. Despite the available molecular architecture of the Na/K-ATPases, a complete molecular mechanism by which the Na and K ions access into and are released from the pump remains unknown. Here we report five cryo-electron microscopy (cryo-EM) structures of the human alpha3 Na/K-ATPase in its cytoplasmic side-open (E1), ATP-bound cytoplasmic side-open (E1•ATP), ADP-AlF trapped Na-occluded (E1•P-ADP), BeF trapped exoplasmic side-open (E2P) and MgF trapped K-occluded (E2•P) states. Our work reveals the atomically resolved structural detail of the cytoplasmic gating mechanism of the Na/K-ATPase.
P2 型 ATP 酶钠钾泵（Na/K-ATPases）是离子转运酶，利用 ATP 将 Na 和 K 逆电化学梯度转运到脂质双层的相反侧，以维持所有动物细胞的膜离子浓度梯度。尽管 Na/K-ATPases 的分子结构已经确定，但 Na 和 K 离子进入和离开泵的完整分子机制仍不清楚。本文报道了 5 种人源α3 Na/K-ATPase 在细胞质侧开放（E1）、ATP 结合的细胞质侧开放（E1•ATP）、ADP-AlF 捕获的 Na 内陷（E1•P-ADP）、BeF 捕获的胞外侧开放（E2P）和 MgF 捕获的 K 内陷（E2•P）状态的冷冻电镜（cryo-EM）结构。本研究揭示了 Na/K-ATPase 细胞质门控机制的原子分辨率结构细节。
Zotero 插件