First Nucleotide-Binding Domain of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR NBD1)

The first nucleotide-binding domain (NBD1) is one of two ATP-binding cassette (ABC) domains in the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that functions as a phosphorylation- and ATP-gated chloride channel in epithelial cells. CFTR is unique among ABC transporters because it acts as an ion channel rather than a transporter, with its gating regulated by ATP binding and hydrolysis at the NBDs, and by phosphorylation events. The most prevalent mutation causing cystic fibrosis (ΔF508; deletion of phenylalanine at position 508) occurs within NBD1. This residue lies on an interface thought critical for communication between NBDs and TMDs during gating transitions. Its loss disrupts folding/stability/trafficking/functionality leading to disease phenotype.

ATP binding and hydrolysis modulate CFTR channel gating.