Structural insights into the mechanism of pancreatic KATP 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 channe...

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Vydáno v:Nature communications Ročník 13; číslo 1; s. 2770 - 10
Hlavní autoři: Wang, Mengmeng, Wu, Jing-Xiang, Ding, Dian, Chen, Lei
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 19.05.2022
Nature Publishing Group
Nature Portfolio
Témata:
101/28
631/154/436
631/45/269/1151
631/535/1258/1259
692/699/2743/137
82/83
9/74
ABC transporters
Adenosine diphosphate
Adenosine triphosphate
Channels
Diabetes
Excitability
Humanities and Social Sciences
Hypoglycemia
Insulin
Intracellular
Laboratories
Metabolism
multidisciplinary
Mutation
Nucleotides
Pancreas
Physiology
Potassium
Potassium channels (inwardly-rectifying)
Proteins
Science
Science (multidisciplinary)
Sensors
ISSN:2041-1723, 2041-1723
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Shrnutí: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. K ATP channels are energy sensors. Here, authors report the Cryo-EM structures of pancreatic K ATP in both the closed state and the pre-open state. These structures illuminate the mechanism of K ATP channel regulation by the intracellular nucleotides.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-30430-4