ATP-sensitive potassium (KATP) channels have crucial roles in several biological processes. KATP channels possess four regulatory sulfonylurea receptors. The SUR proteins are members of the ubiquitous ATP-binding cassette (ABC) superfamily. However, unlike most ABC proteins, SURs do not transport substrates but function strictly as regulators of KATP channel activity. Currently, studies into the molecular basis by which various mutations in SUR2A cause disease are highly limited. This is primarily a consequence of poor solubility of isolated SUR2A NBDs, as is typical for many eukaryotic NBDs. By employing structure-based sequence alignments and biophysical studies, we determined domain boundaries for SUR2A NBD1 that enabled, for the first time, NMR studies of NBD1. Our biophysical studies demonstrate that the isolated SUR2A NBD1 is folded and exhibits differential dynamics upon ATP binding activity. Additional studies are now possible to examine the effects of disease-causing mutations on structure, dynamics, and interactions of NBD1.MAS
