Background: Cystic fibrosis transmembrane conductance regulator (CFTR) has adenylate kinase activity (ATP + AMP ⇆ 2 ADP).Results: ATP enables CFTR photolabeling by 8-N3-AMP, and AMP increases 8-N3-ATP photolabeling at ATP-binding site 2.Conclusion: AMP interacts with CFTR in an ATP-dependent manner and alters ATP interaction with the adenylate kinase active center ATP-binding site.Significance: These findings exemplify nucleotide interactions with an ABC adenylate kinase.

Background: Electrophysiological studies indicated that Cl− channel function of cystic fibrosis transmembrane conductance regulator (CFTR) can be coupled to adenylate kinase activity (ATP+AMP ⇆ 2 ADP).Results: CFTR catalyzes phosphoryl group transfer between a nucleotide triphosphate and a photoactivatable AMP analog.Conclusion: CFTR exhibits adenylate kinase activity.Significance: These data demonstrate biochemically that a membrane-bound ABC transporter can function as an adenylate kinase.

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) channels have ATPase and adenylate kinase activity.Results: Mutating Gln-1291 disrupts adenylate kinase- but not ATPase-dependent gating, and it reduces channel activity in airway epithelia.Conclusion: Normal CFTR function in airway epithelia may depend on its adenylate kinase activity.Significance: Adenylate kinase activity is important for the function of an ATP-binding cassette transporter.