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


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.

Extracted Key Phrases

7 Figures and Tables

Citations per Year

532 Citations

Semantic Scholar estimates that this publication has 532 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@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} }