Cystic fibrosis transmembrane conductance regulator first nucleotide-binding domain (CFTR NBD1)

The cystic fibrosis transmembrane conductance regulator first nucleotide-binding domain (CFTR NBD1) is one of two key cytosolic ATP-binding domains in the CFTR protein, an ATP-binding cassette (ABC) family member that acts as a chloride and bicarbonate ion channel at the apical membrane of epithelial cells[1][3][6]. The NBD1 domain contains critical motifs required for ATP binding and hydrolysis, directly regulating channel gating—ATP binding at NBD1 (together with NBD2) induces channel opening, while hydrolysis and subsequent ATP release closes the channel[1][4][3]. NBD1 is of exceptional clinical importance because it houses the site of the most common CF-causing mutation, ΔF508, which disrupts protein folding, stability, and trafficking, leading to defective chloride transport and the multisystem disease cystic fibrosis[1][3][6]. Drugs that act as correctors (restoring protein folding and cellular trafficking) and potentiators (increasing the probability of channel opening) directly or indirectly target defects associated with this domain, making it a validated therapeutic target for cystic fibrosis[2][3][10].

Other names

NBD1 of CFTRCFTR NBD1nucleotide-binding domain 1 of CFTR

Potentiation of CFTR channel activity (e.g., facilitating channel opening) Correction/stabilization of protein folding and trafficking Enhancement of cell surface expression and function of mutant CFTR