Structural insights into the mechanism of pancreatic K<sub>ATP</sub> channel regulation by nucleotides.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35589716.
- Also identified by DOI 10.1038/s41467-022-30430-4 and PMC identifier 9120461.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
ATP-sensitive potassium channels (K<sub>ATP</sub>) are metabolic sensors that convert the intracellular ATP/ADP ratio to the excitability of cells. They are involved in many physiological processes and implicated in several human diseases. Here we present the cryo-EM structures of the pancreatic K<sub>ATP</sub> channel in both the closed state and the pre-open state, resolved in the same sample. We observe the binding of nucleotides at the inhibitory sites of the Kir6.2 channel in the closed but not in the pre-open state. Structural comparisons reveal the mechanism for ATP inhibition and Mg-ADP activation, two fundamental properties of K<sub>ATP</sub> channels. Moreover, the structures also uncover the activation mechanism of diazoxide-type K<sub>ATP</sub> openers.
Medical subject headings
- Adenosine Triphosphate
- KATP Channels