核苷酸调节胰腺 K 通道机制的结构见解。

State Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, 100871, Beijing, China.

Peking-Tsinghua Center for Life Sciences, Peking University, 100871, Beijing, China.

Nat Commun. 2022 May 19;13(1):2770. doi: 10.1038/s41467-022-30430-4.

ATP-sensitive potassium channels (K) are metabolic sensors that convert the intracellular ATP/ADP ratio to the excitability of cells. They are involved in many physiological processes and implicated in several human diseases. Here we present the cryo-EM structures of the pancreatic K channel in both the closed state and the pre-open state, resolved in the same sample. We observe the binding of nucleotides at the inhibitory sites of the Kir6.2 channel in the closed but not in the pre-open state. Structural comparisons reveal the mechanism for ATP inhibition and Mg-ADP activation, two fundamental properties of K channels. Moreover, the structures also uncover the activation mechanism of diazoxide-type K openers.

三磷酸腺苷敏感性钾通道（K）是代谢传感器，可将细胞内的 ATP/ADP 比率转换为细胞的兴奋性。它们参与许多生理过程，并与几种人类疾病有关。在这里，我们展示了在相同样品中解析的处于关闭状态和预开放状态的胰腺 K 通道的冷冻电镜结构。我们观察到核苷酸结合在关闭但不在预开放状态的 Kir6.2 通道的抑制性位点上。结构比较揭示了 ATP 抑制和 Mg-ADP 激活的机制，这是 K 通道的两个基本特性。此外，这些结构还揭示了二氮嗪型 K 通道开放剂的激活机制。