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The structure of KATP H175K mutant in pre-open state
Structural highlights
FunctionKCJ11_MOUSE This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium. Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation (By similarity). Publication Abstract from PubMedATP-sensitive potassium channels (K(ATP)) 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(ATP) 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(ATP) channels. Moreover, the structures also uncover the activation mechanism of diazoxide-type K(ATP) openers. Structural insights into the mechanism of pancreatic K(ATP) channel regulation by nucleotides.,Wang M, Wu JX, Ding D, Chen L Nat Commun. 2022 May 19;13(1):2770. doi: 10.1038/s41467-022-30430-4. PMID:35589716[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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