ABC transporters use ATP to drive conformational changes that move substrates across membranes. The nucleotide-binding domain (NBD) acts as the cytosolic “motor,” sensing and hydrolyzing ATP to ADP, while the transmembrane domain (TMD) forms the membrane pathway and receives signals from the NBD to open and close gates. While many studies have described NBD dimers, this work examines a single NBD of the multidrug exporter BmrA, focusing on how the nucleotide state may influence the arrangement of its two core parts (a RecA-like and an α-helical subdomain) and a conserved hinge tryptophan near the NBD-TMD interface, known to mediate communication between the nucleotide-binding site (NBS) and the TMD. The central finding is an interpretable pattern at the single NBD level: nucleotide-free ensembles favor a resting, more open arrangement stabilized by the hinge, while nucleotide-bound ensembles (both ATP- and ADP-bound) show more compact configurations, with evidence that ADP biases a tighter local packing than ATP. Functionally, the hinge tryptophan and its neighbors appear to act as a tunable spacer, maintaining a baseline distance in the absence of nucleotide and adopting alternative contacts when nucleotide is present. This mechanism may translate NBS occupancy into structural cues that downstream TMD elements can interpret. These results are considered alongside independent experimental findings on intact BmrA, which report nucleotide-sensitive changes near hinge-proximal regions that transmit information between NBD and TMD. The consistency between the single-domain picture and transporter-level data supports a working model in which the conserved hinge encodes nucleotide state into single-domain conformations. Notably, ADP may promote tighter internal-NBD packing than ATP, potentially priming long-range signaling toward the membrane in ABC transporters.
Rostami et al. (Sun,) studied this question.