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

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.

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@article{Mikhailov20053DSA, title={3-D structural and functional characterization of the purified KATP channel complex Kir6.2-SUR1.}, author={Michael V Mikhailov and Jeff D Campbell and Heidi de Wet and Kenju Shimomura and Brittany Zadek and Richard F. Collins and Mark S. P. Sansom and Robert Curtis Ford and Frances M. Ashcroft}, journal={The EMBO journal}, year={2005}, volume={24 23}, pages={4166-75} }