5WUA

Structure of a Pancreatic ATP-sensitive Potassium Channel

Summary for 5WUA

• Entry DOI: 10.2210/pdb5wua/pdb
• EMDB information: 6689
• Descriptor: ATP-sensitive inward rectifier potassium channel 11,superfolder GFP, SUR1 (2 entities in total)
• Functional Keywords: katp, channel, abc transporter, kir, transport protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 8
• Total formula weight: 1014543.28

Authors

Li, N.,Wu, J.-X.,Chen, L.,Gao, N. (deposition date: 2016-12-16, release date: 2017-01-25, Last modification date: 2024-11-13)

Primary citation

Li, N.,Wu, J.X.,Ding, D.,Cheng, J.,Gao, N.,Chen, L.
Structure of a Pancreatic ATP-Sensitive Potassium Channel
Cell, 168:101-110.e10, 2017

PubMed Abstract: ATP-sensitive potassium channels (K) 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, we elucidated the structure of a hetero-octameric pancreatic K 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) molecule uncouples Kir6.2 from glibenclamide-bound SUR1. These structural observations suggest a molecular mechanism for K regulation by anti-diabetic sulfonylurea drugs, intracellular adenosine nucleotide concentrations, and PIP lipid.

PubMed: 28086082
DOI: 10.1016/j.cell.2016.12.028

Experimental method

ELECTRON MICROSCOPY (5.6 Å)