Structure of a Pancreatic ATP-Sensitive Potassium Channel
Open accessAbstract
ATP-sensitive potassium channels (K ATP) couple intracellular ATP levels with membrane excitability. These channels play crucial roles in many essential physiological processes and have been implicated extensively in a spectrum of metabolic diseases and disorders. To gain insight into the mechanism of K ATP, we elucidated the structure of a hetero-octameric pancreatic K ATP channel in complex with a non-competitive inhibitor glibenclamide by single-particle cryoelectron microscopy to 5.6-Å resolution. The structure shows that four SUR1 regulatory subunits locate peripherally and dock onto the central Kir6.2 channel tetramer through the SUR1 TMD0-L0 fragment. Glibenclamide-bound SUR1 uses TMD0-L0 fragment to stabilize Kir6.2 channel in a closed conformation. In another structural population, a putative co-purified phosphatidylinositol 4,5-bisphosphate (PIP 2) molecule uncouples Kir6.2 from glibenclamide-bound SUR1. These structural observations suggest a molecular mechanism for K ATP regulation by anti-diabetic sulfonylurea drugs, intracellular adenosine nucleotide concentrations, and PIP 2 lipid.
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The putative ATP-binding site of Kir6.2 sits at the interface between the N-terminus of one subunit and the C-terminus of the other, with the β-phosphate of ATP interacting with residue K185.
“It sits at the interface between the N-terminus of one subunit and the C-terminus of the other, with the β-phosphate of ATP interacting with residue K185.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [393]
The Results and Discussion (page not provided) place K185 in a positively charged patch beside a cavity that could accommodate ATP and suggest that the patch may interact with ATP phosphate groups. The paper does not specify a β-phosphate–K185 interaction or locate the site at the stated interface between two Kir6.2 subunits; it also says ATP was not added to the sample. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe 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 [393]
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Self-citation
- Authors
- Li, N., Wu, J.-X., Ding, D., Cheng, J., Gao, N., & Chen, L.
- Affiliations
- Peking University (CN)
- Tsinghua University (CN)
- Corresponding author
- Gao, Ning
- Chen, Lei
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 168
- Issue
- 1-2
- Pages
- 101-110.e10
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2575684964
- Cited by
- 252
- References
- 57
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 18 · 2023: 23 · 2022: 21 · 2021: 39 · 2020: 25 · 2019: 26 · 2018: 37 · 2017: 29
- FWCI
- 13.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology of China (2016YFA0502004, 2016YFA0500700, 2013CB910404)
- National Natural Science Foundation of China (31622021, 31521062, 31422016, 31470722, 31630087)
- Young Thousand Talents Program of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- ATP-sensitive potassium channels, Kir6.2, SUR1, glibenclamide, sulfonylurea drugs, phosphatidylinositol 4,5-bisphosphate, channel gating, adenosine nucleotides
- MeSH terms
- Kcnj11 Channel, Animals, Humans, Hydrolases, Mammals, Mesocricetus, Models, Molecular, ATP Binding Cassette Transporter, Subfamily B, Cryoelectron Microscopy, Potassium Channels, Inwardly Rectifying, Mice, KATP Channels, Phosphoinositide Phospholipase C, Sulfonylurea Receptors
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