PMC

Structural modeling of Kir6.1 protein with the incorporation of GSH. The overall structural model of two opposing Kir6.1 monomers (out of four for clarity) was displayed. Boxed area was enlarged and showed the GSH associated area. The GSH moiety occupies a space between the inner and outer helix. The addition of GSH therefore impairs the movement of inner helix, which is necessary for the channel opening. The figure is modified fromJournal of Biological Chemistry with permission ^[].

Model of SUR2B core domains. A: SUR2B core domains (TMD1, 2 and NBD1, 2) are modeled using SAV1866 as a template. Shaded region is plasmic membrane. B: The interface between TMDs and NBDs are highlighted. Intracellular loop-1 (ICL1) of TMD1 physically interacts with NBD1 and NBD2. ICL2 of TMD1 only interacts with NBD2. Thus TMD1 mainly interact with NBD2. Similarly, TMD2 mainly interacts with NBD1. C and D: The three critical residues involved in PKA phosphorylation are highlighted. Note the side chain of Arg1462 is far from phosphorlation residue Ser1387 before phosphorylation. It is attracted by phosphorylated Ser1387 (p-Ser1387) after PKA phosphorylation and forms a tight triad with p-Ser1387 and Tyr506. The figure is modified fromJournal of Biological Chemistry with permission ^[].

Molecular structure of the vascular K_ATP channel. K_ATP channels are octameric complexes formed by 4 Kir6 subunits (Kir6.x) and 4 accessory sulfonylurea receptor (SUR) subunits. The Kir6.x subunit has 2 transmembrane helixes. SUR subunit has 3 transmembrane domains (TMD0, 1 and 2). There are two intracellular loops linking the adjacent TMDs. Each intracellular loop contains a nucleotide binding domain (NBD1 and NBD2, respectively). A Walker A motif (W_A), a Walker B motif (W_B), and a linker region are located within the NBDs. The Ser379, Ser385, Ser391, and Ser397 at the distal C-terminus of Kir6.1 are PKC phosphorylation residues. The Ser1387 is PKA phosphorylation residue. The Cys176 in the transmembrane domain of Kir6.1 is the major residue accounting for the channel’s oxidant sensitivity.