Role for SUR2A ED domain in allosteric coupling within the K(ATP) channel complex. J Gen Physiol 2008 Mar;131(3):185-96
Date
02/27/2008Pubmed ID
18299394Pubmed Central ID
PMC2248718DOI
10.1085/jgp.200709852Scopus ID
2-s2.0-40849145619 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
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.
Author List
Karger AB, Park S, Reyes S, Bienengraeber M, Dyer RB, Terzic A, Alekseev AEMESH terms used to index this publication - Major topics in bold
ATP-Binding Cassette TransportersAdenosine Triphosphate
Allosteric Regulation
Cell Line
Humans
Ion Channel Gating
Potassium Channels
Potassium Channels, Inwardly Rectifying
Protein Structure, Tertiary
Receptors, Drug
Sulfonylurea Compounds
Sulfonylurea Receptors
