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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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
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author Wang, Mengmeng
Wu, Jing-Xiang
Ding, Dian
Chen, Lei
author_facet Wang, Mengmeng
Wu, Jing-Xiang
Ding, Dian
Chen, Lei
author_sort Wang, Mengmeng
collection PubMed
description 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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spelling pubmed-91204612022-05-21 Structural insights into the mechanism of pancreatic K(ATP) channel regulation by nucleotides Wang, Mengmeng Wu, Jing-Xiang Ding, Dian Chen, Lei Nat Commun Article 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. Nature Publishing Group UK 2022-05-19 /pmc/articles/PMC9120461/ /pubmed/35589716 http://dx.doi.org/10.1038/s41467-022-30430-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Mengmeng
Wu, Jing-Xiang
Ding, Dian
Chen, Lei
Structural insights into the mechanism of pancreatic K(ATP) channel regulation by nucleotides
title Structural insights into the mechanism of pancreatic K(ATP) channel regulation by nucleotides
title_full Structural insights into the mechanism of pancreatic K(ATP) channel regulation by nucleotides
title_fullStr Structural insights into the mechanism of pancreatic K(ATP) channel regulation by nucleotides
title_full_unstemmed Structural insights into the mechanism of pancreatic K(ATP) channel regulation by nucleotides
title_short Structural insights into the mechanism of pancreatic K(ATP) channel regulation by nucleotides
title_sort structural insights into the mechanism of pancreatic k(atp) channel regulation by nucleotides
topic Article
url 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
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