| Title | Structural insights into the mechanism of pancreatic K-ATP channel regulation by nucleotides |
| Authors | Wang, Mengmeng Wu, Jing-Xiang Ding, Dian Chen, Lei |
| Affiliation | Peking Univ, Beijing Key Lab Cardiometabol Mol Med, Inst Mol Med, Coll Future Technol,State Key Lab Membrane Biol, Beijing 100871, Peoples R China Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China Peking Univ, Natl Biomed Imaging Ctr, Beijing 100871, Peoples R China |
| Keywords | CRYO-EM MUTATIONS KIR6.2 SENSITIVITY REFINEMENT ACTIVATION BINDING SUR1 PIP2 |
| Issue Date | 19-May-2022 |
| Publisher | NATURE COMMUNICATIONS |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/646716 |
| DOI | 10.1038/s41467-022-30430-4 |
| Indexed | SCI(E) |
| Appears in Collections: | 分子医学研究所 膜生物学国家重点实验室 生命科学学院 前沿交叉学科研究院 |
