Sulphonylurea receptors regulate the channel pore in ATP-sensitive potassium channels via an inter-subunit salt bridge

ATP-sensitive potassium channels play key roles in many tissues by coupling metabolic status to membrane potential. In contrast to other potassium channels, the pore-forming Kir6 subunits must co-assemble in hetero-octameric complexes with ABC family sulphonylurea receptor (SUR) subunits to facilitate cell surface expression. Binding of nucleotides and drugs to SUR regulates channel gating but how these responses are communicated within the complex, has remained elusive. We have now identified an electrostatic interaction, forming part of a functional interface between the cytoplasmic nucleotide binding domain-2 of SUR2 subunits and the distal C-terminus of Kir6 polypeptides, that determines channel response to nucleotide, potassium channel opener and antagonist. Mutation of participating residues disrupted physical interaction and regulation of expressed channels, properties that were restored in paired charge-swop mutants. Equivalent interactions were identified in Kir6.1 and Kir6.2 containing channels suggesting a conserved mechanism of allosteric regulation.

Source: BJ Cell - September 19, 2014 Category: Biochemistry Authors: D Lodwick, R D Rainbow, H N Rubaiy, M Al Johi, G W Vuister, R I Norman Tags: BJ Energy Source Type: research