InterPro domain: IPR003018

The GAF domain is named after some of the proteins it is found in, including cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA. It is also found in and guanylyl cyclases and phytochromes [ 1 , 2 ]. The structure of a GAF domain shows that the domain shares a similar fold with the PAS domain [ 3 ]. Adenylyl and guanylyl cyclases catalyse ATP and GTP to the second messengers cAMP and cGMP respectively, these products up-regulating catalytic activity by binding to the regulatory GAF domain(s). The opposite hydrolysis reaction is catalysed by phosphodiesterase. cGMP-dependent 3',5'-cyclic phosphodiesterase catalyses the conversion of guanosine 3',5'-cyclic phosphate to guanosine 5'-phosphate. Here too, cGMP regulates catalytic activity by GAF-domain binding. Phytochromes are regulatory photoreceptors in plants and bacteria which exist in two thermally stable states that are reversibly inter-convertible by light, the Pr state absorbs maximally in the red region of the spectrum, while the Pfr state absorbs maximally in the far-red region [ 4 ].

The GAF domain is also found in FhlA (formate hydrogen lyase transcriptional activator) and NifA, a transcriptional activator required for activation of most Nif operons, which are directly involved in nitrogen fixation. NifA interacts with sigma-54 [ 5 ].

1. The GAF domain: an evolutionary link between diverse phototransducing proteins. Trends Biochem. Sci. 22, 458-9
2. Cyclic nucleotide binding GAF domains from phosphodiesterases: structural and mechanistic insights. Structure 17, 1551-7
3. Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor. EMBO J. 19, 5288-99
4. Phytochrome three-dimensional structures and functions. Biochem. Soc. Trans. 38, 710-6
5. Role of integration host factor in stimulating transcription from the sigma 54-dependent nifH promoter. J. Mol. Biol. 227, 602-20