Structural insights into the mechanism of pancreatic K(ATP) channel regulation by nucleotides

ATP-sensitive potassium channels (K(ATP)) 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(ATP) chann...

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Detalles Bibliográficos
Autores principales: Wang, Mengmeng, Wu, Jing-Xiang, Ding, Dian, Chen, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120461/
https://www.ncbi.nlm.nih.gov/pubmed/35589716
http://dx.doi.org/10.1038/s41467-022-30430-4
Descripción
Sumario:ATP-sensitive potassium channels (K(ATP)) 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(ATP) 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(ATP) channels. Moreover, the structures also uncover the activation mechanism of diazoxide-type K(ATP) openers.

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