Referenced in: none

Automatically associated channels: Kir6.2

Title: 3-D structural and functional characterization of the purified KATP channel complex Kir6.2-SUR1.

Authors: Michael V Mikhailov, Jeff D Campbell, Heidi de Wet, Kenju Shimomura, Brittany Zadek, Richard F Collins, Mark S P Sansom, Robert C Ford, Frances M Ashcroft

Journal, date & volume: EMBO J., 2005 Dec 7 , 24, 4166-75

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16308567

Abstract
ATP-sensitive potassium (K(ATP)) channels conduct potassium ions across cell membranes and thereby couple cellular energy metabolism to membrane electrical activity. Here, we report the heterologous expression and purification of a functionally active K(ATP) channel complex composed of pore-forming Kir6.2 and regulatory SUR1 subunits, and determination of its structure at 18 A resolution by single-particle electron microscopy. The purified channel shows ATP-ase activity similar to that of ATP-binding cassette proteins related to SUR1, and supports Rb(+) fluxes when reconstituted into liposomes. It has a compact structure, with four SUR1 subunits embracing a central Kir6.2 tetramer in both transmembrane and cytosolic domains. A cleft between adjacent SUR1s provides a route by which ATP may access its binding site on Kir6.2. The nucleotide-binding domains of adjacent SUR1 appear to interact, and form a large docking platform for cytosolic proteins. The structure, in combination with molecular modelling, suggests how SUR1 interacts with Kir6.2.