NBDS

NBDs, or nucleotide-binding domains, are conserved protein domains that bind and hydrolyze nucleotide triphosphates, most commonly ATP or GTP. They function as energy transducers that drive conformational changes essential for the activity of many proteins, including transporters, helicases, and motor enzymes. In many proteins, an NBD is one module among others, forming a modular architecture that couples nucleotide hydrolysis to substrate processing, transport, or remodeling activities.

Most NBDs belong to the P-loop NTPase superfamily and contain several conserved motifs. The Walker A motif binds the phosphate groups of the nucleotide, while the Walker B motif coordinates a water molecule and magnesium to catalyze hydrolysis. In ABC transporters, an additional ABC signature motif, LSGGQ, helps couple ATP binding and hydrolysis to substrate translocation. NBDs can function as monomers or form functional dimers; in ABC transporters, two NBDs come together to create a composite ATPase site.

NBDs are widespread across life and appear in diverse systems. Major examples include bacterial and eukaryotic ABC transporters that export or import substrates across membranes, the N domains of P-type ATPases, and ATPase domains within helicases that unwind nucleic acids. In transporters, ATP hydrolysis in the NBDs is mechanically linked to movements of other domains that drive substrate translocation or remodeling. Dysfunctions or dysregulation of NBDs can impact transport efficiency, energy metabolism, and cellular homeostasis, with implications for health and disease.