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The Nucleotide-Binding Sites of SUR1: A Mechanistic Model
ATP-sensitive potassium (K(ATP)) channels comprise four pore-forming Kir6.2 subunits and four modulatory sulfonylurea receptor (SUR) subunits. The latter belong to the ATP-binding cassette family of transporters. K(ATP) channels are inhibited by ATP (or ADP) binding to Kir6.2 and activated by Mg-nuc...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Biophysical Society
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699857/ https://www.ncbi.nlm.nih.gov/pubmed/26682803 http://dx.doi.org/10.1016/j.bpj.2015.10.026 |
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author | Vedovato, Natascia Ashcroft, Frances M. Puljung, Michael C. |
author_facet | Vedovato, Natascia Ashcroft, Frances M. Puljung, Michael C. |
author_sort | Vedovato, Natascia |
collection | PubMed |
description | ATP-sensitive potassium (K(ATP)) channels comprise four pore-forming Kir6.2 subunits and four modulatory sulfonylurea receptor (SUR) subunits. The latter belong to the ATP-binding cassette family of transporters. K(ATP) channels are inhibited by ATP (or ADP) binding to Kir6.2 and activated by Mg-nucleotide interactions with SUR. This dual regulation enables the K(ATP) channel to couple the metabolic state of a cell to its electrical excitability and is crucial for the K(ATP) channel’s role in regulating insulin secretion, cardiac and neuronal excitability, and vascular tone. Here, we review the regulation of the K(ATP) channel by adenine nucleotides and present an equilibrium allosteric model for nucleotide activation and inhibition. The model can account for many experimental observations in the literature and provides testable predictions for future experiments. |
format | Online Article Text |
id | pubmed-4699857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Biophysical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-46998572016-12-15 The Nucleotide-Binding Sites of SUR1: A Mechanistic Model Vedovato, Natascia Ashcroft, Frances M. Puljung, Michael C. Biophys J Biophysical Perspective ATP-sensitive potassium (K(ATP)) channels comprise four pore-forming Kir6.2 subunits and four modulatory sulfonylurea receptor (SUR) subunits. The latter belong to the ATP-binding cassette family of transporters. K(ATP) channels are inhibited by ATP (or ADP) binding to Kir6.2 and activated by Mg-nucleotide interactions with SUR. This dual regulation enables the K(ATP) channel to couple the metabolic state of a cell to its electrical excitability and is crucial for the K(ATP) channel’s role in regulating insulin secretion, cardiac and neuronal excitability, and vascular tone. Here, we review the regulation of the K(ATP) channel by adenine nucleotides and present an equilibrium allosteric model for nucleotide activation and inhibition. The model can account for many experimental observations in the literature and provides testable predictions for future experiments. The Biophysical Society 2015-12-15 2015-12-15 /pmc/articles/PMC4699857/ /pubmed/26682803 http://dx.doi.org/10.1016/j.bpj.2015.10.026 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Biophysical Perspective Vedovato, Natascia Ashcroft, Frances M. Puljung, Michael C. The Nucleotide-Binding Sites of SUR1: A Mechanistic Model |
title | The Nucleotide-Binding Sites of SUR1: A Mechanistic Model |
title_full | The Nucleotide-Binding Sites of SUR1: A Mechanistic Model |
title_fullStr | The Nucleotide-Binding Sites of SUR1: A Mechanistic Model |
title_full_unstemmed | The Nucleotide-Binding Sites of SUR1: A Mechanistic Model |
title_short | The Nucleotide-Binding Sites of SUR1: A Mechanistic Model |
title_sort | nucleotide-binding sites of sur1: a mechanistic model |
topic | Biophysical Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699857/ https://www.ncbi.nlm.nih.gov/pubmed/26682803 http://dx.doi.org/10.1016/j.bpj.2015.10.026 |
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