3‐D structural and functional characterization of the purified KATP channel complex Kir6.2–SUR1
Open accessAbstract
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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The KATP channel complex has SUR1 subunits arranged around a central tetrameric Kir6.2 pore.
“The structure of the KATP channel complex reveals the SUR1 subunits are arranged around a central tetrameric Kir6.2 pore (393, 432, 450) (Figure 7B,C).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [450]
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Cites
Association and Stoichiometry of KATP Channel Subunits
Clement, J. P., Kunjilwar, K., Gonzalez, G., Schwanstecher, M., Panten, U., Aguilar-Bryan, L., & Bryan, J. (1997) · Neuron · doi:10.1016/s0896-6273(00)80321-9 · Cited by 692 · see citing works
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Research works printed but not linked: 1
- Masia R, Enkvetchakul D, Nichols CG (2005) Differential nucleotide regulation of K ATP channels by SUR1 and SUR2A. J Mol Cell Cardiol (advance online publication 10 May 2005; doi:10.1016/ j.yjmcc.2005.03.009) · DOI
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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
Self-citationStructure of a Pancreatic ATP-Sensitive Potassium Channel
Li, N., Wu, J.-X., Ding, D., Cheng, J., Gao, N., & Chen, L. (2017) · Cell · doi:10.1016/j.cell.2016.12.028 · Cited by 252 · see citing works
New insights into KATP channel gene mutations and neonatal diabetes mellitus
Pipatpolkai, T., Usher, S., Stansfeld, P. J., & Ashcroft, F. M. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0351-y · Cited by 122 · see citing works
Self-citationHow ATP Inhibits the Open KATP Channel
Craig, T. J., Ashcroft, F. M., & Proks, P. (2008) · The Journal of General Physiology · doi:10.1085/jgp.200709874 · Cited by 67 · see citing works
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- Authors
- Mikhailov, M. V., Campbell, J. D., de Wet, H., Shimomura, K., Zadek, B., Collins, R. F., Sansom, M. S., Ford, R. C., & Ashcroft, F. M.
- Affiliations
- University of Oxford (GB)
- University of Manchester (GB)
- Corresponding author
- Ashcroft, Frances M
- Venue
- The EMBO Journal
- Published
- 2005-11-24
- Volume
- 24
- Issue
- 23
- Pages
- 4166-4175
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- OpenAlex
- W2139404258
- Cited by
- 168
- References
- 1
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 9 · 2020: 6 · 2019: 4 · 2018: 6 · 2017: 9 · 2016: 3 · 2015: 7 · 2014: 13 · 2013: 13 · 2012: 15
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- GlaxoSmithKline
- Wellcome Trust
- Royal Society
- Diabetes UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- ATP-sensitive potassium channels, Kir6.2, SUR1, channel structure, ATPase activity, nucleotide-binding domain, ATP binding site, heterologous expression, protein purification, single-particle electron microscopy
- MeSH terms
- Kcnj11 Channel, Amino Acid Sequence, Animals, Molecular Sequence Data, Receptors, Drug, Recombinant Fusion Proteins, Potassium Channels, Protein Structure, Tertiary, ATP-Binding Cassette Transporters, Cryoelectron Microscopy, Potassium Channels, Inwardly Rectifying, Mice, Rats, Sulfonylurea Receptors
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