Remodeling of the cytoplasmic SUR1-Kir6.2 interface from ATP-inhibited to open conformation. (A) Overlay of the Repa/ATP bound closed K_ATP structure in CTD-up conformation (PBD ID 7TYS; blue) and the open Kir6.2^{G334D, C166S} structure (PDB ID 7S5X; yellow). The red box indicates regions shown in closeup, top-down view in B and C. (B and C) Comparison of key molecular differences between ATP-bound closed conformation (B) and SUR1 NBD-dimerized, Kir6.22^{G334D, C166S} open conformation (C). Note the reorientation of the F60 and F168 side chains and the enlargement of the helix bundle crossing gate in the open conformation (red circle). The distances between Q52 of Kir6.2 and E203 or K205 of SUR1-L0 (red dashed lines) are also significantly increased in the open conformation, which disfavors ATP binding.