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  • Title: Structural insights into the mechanism of pancreatic KATP channel regulation by nucleotides.
    Author: Wang M, Wu JX, Ding D, Chen L.
    Journal: Nat Commun; 2022 May 19; 13(1):2770. PubMed ID: 35589716.
    Abstract:
    ATP-sensitive potassium channels (KATP) 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 KATP 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 KATP channels. Moreover, the structures also uncover the activation mechanism of diazoxide-type KATP openers.
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