[HTML][HTML] Cantu syndrome–associated SUR2 (ABCC9) mutations in distinct structural domains result in KATP channel gain-of-function by differential mechanisms

C McClenaghan, A Hanson, M Sala-Rabanal… - Journal of Biological …, 2018 - ASBMB
The complex disorder Cantu syndrome (CS) arises from gain-of-function mutations in either
KCNJ8 or ABCC9, the genes encoding the Kir6. 1 and SUR2 subunits of ATP-sensitive
potassium (K ATP) channels, respectively. Recent reports indicate that such mutations can
increase channel activity by multiple molecular mechanisms. In this study, we determined
the mechanism by which K ATP function is altered by several substitutions in distinct
structural domains of SUR2: D207E in the intracellular L0-linker and Y985S, G989E …