The dynamic interplay of PIP₂ and ATP in the regulation of the K_ATP channel.

ABSTRACT: ATP-sensitive potassium (K_ATP ) channels couple the intracellular ATP concentration to insulin secretion. K_ATP channel activity is inhibited by ATP binding to the Kir6.2 tetramer and activated by phosphatidylinositol 4,5-bisphosphate (PIP₂ ). Here, we use molecular dynamics simulation, electrophysiology and fluorescence spectroscopy to show that ATP and PIP₂ occupy different binding pockets that share a single amino acid residue, K39. When both ligands are present, simulations suggest that K39 shows a greater preference to co-ordinate with PIP₂ than with ATP. They also predict that a neonatal diabetes mutation at K39 (K39R) increases the number of hydrogen bonds formed between K39 and PIP₂ , potentially accounting for the re

SUBMITTER: Pipatpolkai T 

PROVIDER: S-EPMC9825998 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature