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Role for SUR2A ED Domain in Allosteric Coupling within the K(ATP) Channel Complex
Allosteric regulation of heteromultimeric ATP-sensitive potassium (K(ATP)) channels is unique among protein systems as it implies transmission of ligand-induced structural adaptation at the regulatory SUR subunit, a member of ATP-binding cassette ABCC family, to the distinct pore-forming K(+) (Kir6....
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248718/ https://www.ncbi.nlm.nih.gov/pubmed/18299394 http://dx.doi.org/10.1085/jgp.200709852 |
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author | Karger, Amy B. Park, Sungjo Reyes, Santiago Bienengraeber, Martin Dyer, Roy B. Terzic, Andre Alekseev, Alexey E. |
author_facet | Karger, Amy B. Park, Sungjo Reyes, Santiago Bienengraeber, Martin Dyer, Roy B. Terzic, Andre Alekseev, Alexey E. |
author_sort | Karger, Amy B. |
collection | PubMed |
description | Allosteric regulation of heteromultimeric ATP-sensitive potassium (K(ATP)) channels is unique among protein systems as it implies transmission of ligand-induced structural adaptation at the regulatory SUR subunit, a member of ATP-binding cassette ABCC family, to the distinct pore-forming K(+) (Kir6.x) channel module. Cooperative interaction between nucleotide binding domains (NBDs) of SUR is a prerequisite for K(ATP) channel gating, yet pathways of allosteric intersubunit communication remain uncertain. Here, we analyzed the role of the ED domain, a stretch of 15 negatively charged aspartate/glutamate amino acid residues (948–962) of the SUR2A isoform, in the regulation of cardiac K(ATP) channels. Disruption of the ED domain impeded cooperative NBDs interaction and interrupted the regulation of K(ATP) channel complexes by MgADP, potassium channel openers, and sulfonylurea drugs. Thus, the ED domain is a structural component of the allosteric pathway within the K(ATP) channel complex integrating transduction of diverse nucleotide-dependent states in the regulatory SUR subunit to the open/closed states of the K(+)-conducting channel pore. |
format | Text |
id | pubmed-2248718 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22487182008-09-01 Role for SUR2A ED Domain in Allosteric Coupling within the K(ATP) Channel Complex Karger, Amy B. Park, Sungjo Reyes, Santiago Bienengraeber, Martin Dyer, Roy B. Terzic, Andre Alekseev, Alexey E. J Gen Physiol Articles Allosteric regulation of heteromultimeric ATP-sensitive potassium (K(ATP)) channels is unique among protein systems as it implies transmission of ligand-induced structural adaptation at the regulatory SUR subunit, a member of ATP-binding cassette ABCC family, to the distinct pore-forming K(+) (Kir6.x) channel module. Cooperative interaction between nucleotide binding domains (NBDs) of SUR is a prerequisite for K(ATP) channel gating, yet pathways of allosteric intersubunit communication remain uncertain. Here, we analyzed the role of the ED domain, a stretch of 15 negatively charged aspartate/glutamate amino acid residues (948–962) of the SUR2A isoform, in the regulation of cardiac K(ATP) channels. Disruption of the ED domain impeded cooperative NBDs interaction and interrupted the regulation of K(ATP) channel complexes by MgADP, potassium channel openers, and sulfonylurea drugs. Thus, the ED domain is a structural component of the allosteric pathway within the K(ATP) channel complex integrating transduction of diverse nucleotide-dependent states in the regulatory SUR subunit to the open/closed states of the K(+)-conducting channel pore. The Rockefeller University Press 2008-03 /pmc/articles/PMC2248718/ /pubmed/18299394 http://dx.doi.org/10.1085/jgp.200709852 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Karger, Amy B. Park, Sungjo Reyes, Santiago Bienengraeber, Martin Dyer, Roy B. Terzic, Andre Alekseev, Alexey E. Role for SUR2A ED Domain in Allosteric Coupling within the K(ATP) Channel Complex |
title | Role for SUR2A ED Domain in Allosteric Coupling within the K(ATP) Channel Complex |
title_full | Role for SUR2A ED Domain in Allosteric Coupling within the K(ATP) Channel Complex |
title_fullStr | Role for SUR2A ED Domain in Allosteric Coupling within the K(ATP) Channel Complex |
title_full_unstemmed | Role for SUR2A ED Domain in Allosteric Coupling within the K(ATP) Channel Complex |
title_short | Role for SUR2A ED Domain in Allosteric Coupling within the K(ATP) Channel Complex |
title_sort | role for sur2a ed domain in allosteric coupling within the k(atp) channel complex |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248718/ https://www.ncbi.nlm.nih.gov/pubmed/18299394 http://dx.doi.org/10.1085/jgp.200709852 |
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