Sulfonylurea receptor 2 (SUR2), intricate sensors for intracellular Mg-nucleotides

SUR2, similar to SUR1, is a regulatory subunit of the ATP-sensitive potassium channel (KATP), which plays a key role in numerous important physiological processes and is implicated in various diseases. Recent structural studies have revealed that, like SUR1, SUR2 can undergo ligand-dependent dynamic conformational changes, transitioning between an inhibitory inward-facing conformation and an activating occluded conformation. In addition, SUR2 possesses a unique inhibitory Regulatory helix (R helix) that is absent in SUR1. The binding of the activating Mg-ADP to NBD2 of SUR2 competes with the inhibitory Mg-ATP, thereby promoting the release of the R helix and initiating the activation process. Moreover, the signal generated by Mg-ADP binding to NBD2 might be directly transmitted to the TMD of SUR2, prior to NBD dimerization. Furthermore, the C-terminal 42 residues (C42) of SUR2 might allosterically regulate the kinetics of Mg-nucleotide binding on NBD2. These distinctive properties render SUR2 intricate sensors for intracellular Mg-nucleotides.