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bioRxiv · 10.1101/2021.11.29.470334

Structural insights into the mechanism of nucleotide regulation of pancreatic KATP channel

Wang, M.·Wu, J.-X.·Ding, D.·Duan, X.·Ma, S.·Lai, L.·Chen, L.
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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. The nucleotides bind at the inhibitory sites of the Kir6.2 channel in the closed state 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 structure also uncovers the activation mechanism of diazoxide-type KATP openers.

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Wang, M., Wu, J.-X., Ding, D., Duan, X., Ma, S., Lai, L., Chen, L.. 2021-11-29. Structural insights into the mechanism of nucleotide regulation of pancreatic KATP channel. https://doi.org/10.1101/2021.11.29.470334

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