ArticleThe Journal of biological chemistry2015
Structurally distinct ligands rescue biogenesis defects of the KATP channel complex via a converging mechanism.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Article
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- Structure of an open KNature communications · 2024Article
- Mechanistic insights on KATP channel regulation from cryo-EM structures.The Journal of general physiology · 2023Review
- KFrontiers in endocrinology · 2023Review
- Ligand-mediated Structural Dynamics of a Mammalian Pancreatic KJournal of molecular biology · 2022Article
- Kir6.1 and SUR2B in Cantú syndrome.American journal of physiology. Cell physiology · 2022Review
- Subcellular trafficking and endocytic recycling of KAmerican journal of physiology. Cell physiology · 2022Review
- Carbamazepine promotes surface expression of mutant Kir6.2-A28V ATP-sensitive potassium channels by modulating Golgi retention and autophagy.The Journal of biological chemistry · 2022Article
- Vascular KProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Production and purification of ATP-sensitive potassium channel particles for cryo-electron microscopy.Methods in enzymology · 2021Article
- Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management.Reviews in endocrine & metabolic disorders · 2020Review
- Structural Determinants of Insulin Release: Disordered N-Terminal Tail of Kir6.2 Affects Potassium Channel Dynamics through Interactions with Sulfonylurea Binding Region in a SUR1 Partner.The journal of physical chemistry. B · 2020Article
- Ion Channels of the Islets in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Pharmacological chaperones of ATP-sensitive potassium channels: Mechanistic insight from cryoEM structures.Molecular and cellular endocrinology · 2020Review
- Article
- Functional characterization of activating mutations in the sulfonylurea receptor 1 (ABCC8) causing neonatal diabetes mellitus in Asian Indian children.Pediatric diabetes · 2019Article
- Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels.Protein & cell · 2018Article
- Anti-diabetic drug binding site in a mammalian KeLife · 2017Article
- Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating.eLife · 2017Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Small molecules that correct protein misfolding and misprocessing defects offer a potential therapy for numerous human diseases. However, mechanisms underlying pharmacological correction of such defects, especially in heteromeric complexes with structurally diverse constituent proteins, are not well understood. Here we investigate how two chemically distinct compounds, glibenclamide and carbamazepine, correct biogenesis defects in ATP-sensitive potassium (KATP) channels composed of sulfonylurea receptor 1 (SUR1) and Kir6.2. We present evidence that despite structural differences, carbamazepine and glibenclamide compete for binding to KATP channels, and both drugs share a binding pocket in SUR1 to exert their effects. Moreover, both compounds engage Kir6.2, in particular the distal N terminus of Kir6.2, which is involved in normal channel biogenesis, for their chaperoning effects on SUR1 mutants. Conversely, both drugs can correct channel biogenesis defects caused by Kir6.2 mutations in a SUR1-dependent manner. Using an unnatural, photocross-linkable amino acid, azidophenylalanine, genetically encoded in Kir6.2, we demonstrate in living cells that both drugs promote interactions between the distal N terminus of Kir6.2 and SUR1. These findings reveal a converging pharmacological chaperoning mechanism wherein glibenclamide and carbamazepine stabilize the heteromeric subunit interface critical for channel biogenesis to overcome defective biogenesis caused by mutations in individual subunits.
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