Journal Article

Structural insights into the mechanism of pancreatic KATP channel regulation by nucleotides

Ding, Dian, Wu, Jing-Xiang, Wang, Mengmeng, Chen, Lei

2022

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 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