GAF Domains: Two–Billion–Year–Old Molecular Switches that Bind Cyclic Nucleotides

The arrangement of GAF, PAS, and catalytic domains in cyclic nucleotide phosphodiesterases and the cyanobacterial adenylyl cyclase. Nearly all of the PDEs that have been identified to date show the illustrated order of domain arrangement: two GAF domains followed by a catalytic domain. The GAF domain that is more proximal to the N terminus is designated “GAF A,” and the more distal “GAF B.” A similar arrangement is found in the cyanobacterial adenylyl cyclase, although here a PAS domain intervenes between the GAF B and the catalytic domains.