Role for SUR2A ED domain in allosteric coupling within the KATP channel complex

Amy B. Karger, Sungjo Park, Santiago Reyes, Martin Bienengraeber, Roy B. Dyer, Andre Terzic, Alexey E. Alekseev

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 KATP channels. Disruption of the ED domain impeded cooperative NBDs interaction and interrupted the regulation of KATP channel complexes by MgADP, potassium channel openers, and sulfonylurea drugs. Thus, the ED domain is a structural component of the allosteric pathway within the KATP 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.

Original languageEnglish (US)
Pages (from-to)185-196
Number of pages12
JournalJournal of General Physiology
Volume131
Issue number3
DOIs
StatePublished - Mar 2008

ASJC Scopus subject areas

  • Physiology

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    Karger, A. B., Park, S., Reyes, S., Bienengraeber, M., Dyer, R. B., Terzic, A., & Alekseev, A. E. (2008). Role for SUR2A ED domain in allosteric coupling within the KATP channel complex. Journal of General Physiology, 131(3), 185-196. https://doi.org/10.1085/jgp.200709852