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- W2921260144 abstract "Abstract ATP-sensitive potassium (K ATP ) channels composed of a pore-forming Kir6.2 potassium channel and a regulatory ABC transporter sulfonylurea receptor 1 (SUR1) regulate insulin secretion in pancreatic β-cells to maintain glucose homeostasis. Mutations that impair channel folding or assembly prevent cell surface expression and cause congenital hyperinsulinism. Structurally diverse K ATP inhibitors have been shown to act as pharmacochaperones to correct mutant channel expression, but the mechanism is unknown. Here, we compare cryoEM structures of K ATP channels bound to pharmacochaperones glibenclamide, repaglinide, and carbamazepine. We found all three drugs bind within a common pocket in SUR1. Further, we found the N-terminus of Kir6.2 inserted within the central cavity of the SUR1 ABC core, adjacent the drug binding pocket. The findings reveal a common mechanism by which diverse compounds stabilize the Kir6.2 N-terminus within the SUR1 ABC core, allowing it to act as a firm “handle” for the assembly of metastable mutant SUR1-Kir6.2 complexes." @default.
- W2921260144 created "2019-03-22" @default.
- W2921260144 creator A5013854148 @default.
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- W2921260144 creator A5060606567 @default.
- W2921260144 creator A5090735854 @default.
- W2921260144 date "2019-03-08" @default.
- W2921260144 modified "2023-09-24" @default.
- W2921260144 title "Mechanism of pharmacochaperoning in KATP channels revealed by cryo-EM" @default.
- W2921260144 cites W1921676712 @default.
- W2921260144 cites W1964737014 @default.
- W2921260144 cites W1973705361 @default.
- W2921260144 cites W1976507289 @default.
- W2921260144 cites W1983011541 @default.
- W2921260144 cites W1998635877 @default.
- W2921260144 cites W2004984180 @default.
- W2921260144 cites W2005253947 @default.
- W2921260144 cites W2008853223 @default.
- W2921260144 cites W2012735248 @default.
- W2921260144 cites W2014342680 @default.
- W2921260144 cites W2015073184 @default.
- W2921260144 cites W2015251758 @default.
- W2921260144 cites W2016061230 @default.
- W2921260144 cites W2018142757 @default.
- W2921260144 cites W2018566925 @default.
- W2921260144 cites W2022446120 @default.
- W2921260144 cites W2025399834 @default.
- W2921260144 cites W2025639562 @default.
- W2921260144 cites W2025695531 @default.
- W2921260144 cites W2027739484 @default.
- W2921260144 cites W2028470175 @default.
- W2921260144 cites W2030323961 @default.
- W2921260144 cites W2033349405 @default.
- W2921260144 cites W2038353863 @default.
- W2921260144 cites W2039442648 @default.
- W2921260144 cites W2040688084 @default.
- W2921260144 cites W2047169350 @default.
- W2921260144 cites W2048406951 @default.
- W2921260144 cites W2049023341 @default.
- W2921260144 cites W2050264979 @default.
- W2921260144 cites W2053943711 @default.
- W2921260144 cites W2061905525 @default.
- W2921260144 cites W2063240158 @default.
- W2921260144 cites W2074026180 @default.
- W2921260144 cites W2074656220 @default.
- W2921260144 cites W2075592013 @default.
- W2921260144 cites W2083584165 @default.
- W2921260144 cites W2089387031 @default.
- W2921260144 cites W2090640604 @default.
- W2921260144 cites W2091881995 @default.
- W2921260144 cites W2100775765 @default.
- W2921260144 cites W2107955565 @default.
- W2921260144 cites W2112820588 @default.
- W2921260144 cites W2118098299 @default.
- W2921260144 cites W2124026197 @default.
- W2921260144 cites W2127630030 @default.
- W2921260144 cites W2127913502 @default.
- W2921260144 cites W2131874671 @default.
- W2921260144 cites W2141591525 @default.
- W2921260144 cites W2148959338 @default.
- W2921260144 cites W2152275899 @default.
- W2921260144 cites W2153134360 @default.
- W2921260144 cites W2156576736 @default.
- W2921260144 cites W2160289208 @default.
- W2921260144 cites W2162016919 @default.
- W2921260144 cites W2166473564 @default.
- W2921260144 cites W2192323341 @default.
- W2921260144 cites W2271635813 @default.
- W2921260144 cites W2277559429 @default.
- W2921260144 cites W2407236892 @default.
- W2921260144 cites W2418037503 @default.
- W2921260144 cites W2432427150 @default.
- W2921260144 cites W2512152297 @default.
- W2921260144 cites W2574882949 @default.
- W2921260144 cites W2575684964 @default.
- W2921260144 cites W2589923912 @default.
- W2921260144 cites W2593511418 @default.
- W2921260144 cites W2594319058 @default.
- W2921260144 cites W2765575729 @default.
- W2921260144 cites W2766472479 @default.
- W2921260144 cites W2766881846 @default.
- W2921260144 cites W2769967182 @default.
- W2921260144 cites W2790564647 @default.
- W2921260144 cites W2791670278 @default.
- W2921260144 cites W2796938801 @default.
- W2921260144 cites W2802204647 @default.
- W2921260144 cites W2887030288 @default.
- W2921260144 cites W2893878927 @default.
- W2921260144 cites W2899714098 @default.
- W2921260144 cites W2906528689 @default.
- W2921260144 cites W2953320394 @default.
- W2921260144 cites W4250622522 @default.
- W2921260144 doi "https://doi.org/10.1101/572297" @default.
- W2921260144 hasPublicationYear "2019" @default.
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