Protein Family Models

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 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]. This domain can bind O2, CO and NO (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043). [1]. 9433123. The GAF domain: an evolutionary link between diverse phototransducing proteins. Aravind L, Ponting CP;. Trends Biochem Sci 1997;22:458-459. [2]. 20004158. Cyclic nucleotide binding GAF domains from phosphodiesterases: structural and mechanistic insights. Heikaus CC, Pandit J, Klevit RE;. Structure. 2009;17:1551-1557. [3]. 11032796. Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor. Ho YS, Burden LM, Hurley JH;. EMBO J. 2000;19:5288-5299. (from Pfam)

Date:

2024-10-16

This domain is present in cGMP-specific phosphodiesterases, adenylyl and guanylyl cyclases, phytochromes, FhlA and NifA. 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. This domain is also found in FhlA (formate hydrogen lyase transcriptional activator) and NifA, a transcriptional activator which is required for activation of most Nif operons which are directly involved in nitrogen fixation. NifA interacts with sigma-54. This domain can bind biliverdine and phycocyanobilin (Matilla et al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043). Discovery and naming of the GAF domain. [1]. 9433123. The GAF domain: an evolutionary link between diverse phototransducing proteins. Aravind L, Ponting CP;. Trends Biochem Sci 1997;22:458-459. [2]. 20004158. Cyclic nucleotide binding GAF domains from phosphodiesterases: structural and mechanistic insights. Heikaus CC, Pandit J, Klevit RE;. Structure. 2009;17:. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-16

This domain is found linked to a wide range of non-homologous domains in a variety of bacteria. It has been shown to be homologous to the adenylyl cyclase catalytic domain [1] and has diguanylate cyclase activity [4]. This observation correlates with the functional information available on two GGDEF-containing proteins, namely diguanylate cyclase and phosphodiesterase A of Acetobacter xylinum, both of which regulate the turnover of cyclic diguanosine monophosphate. In the WspR protein of Pseudomonas aeruginosa, the GGDEF domain acts as a diguanylate cyclase, PDB:3bre, when the whole molecule appears to form a tetramer consisting of two symmetrically-related dimers representing a biological unit. The active site is the GGD/EF motif, buried in the structure, and the cyclic dimeric guanosine monophosphate (c-di-GMP) bind to the inhibitory-motif RxxD on the surface. The enzyme thus catalyses the cyclisation of two guanosine triphosphate (GTP) molecules to one c-di-GMP molecule [6,7,8]. [1]. 11119645. GGDEF domain is homologous to adenylyl cyclase. Pei J, Grishin NV;. Proteins 2001;42:210-216. [2]. 11557134. Novel domains of the prokaryotic two-component signal transduction systems. Galperin MY, Nikolskaya AN, Koonin EV;. FEMS Microbiol Lett 2001;203:11-21. [3]. 15063857. Cyclic di-guanosine-monophosphate comes of age: a novel secondary messenger involved in modulating cell surface structures in bacteria?. Jenal U;. Curr Opin Microbiol 2004;7:185-191. [4]. 15075296. Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain. Paul R, Weiser S, Amiot NC, Chan C, Sch. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-16

sensor domain-containing diguanylate cyclase containing a GAF sensor domain, catalyzes the synthesis of cyclic-di-GMP (c-di-GMP) via the condensation of 2 GTP molecules

Date:

2022-11-17

The GGDEF domain is named for the motif GG[DE]EF shared by many proteins carrying the domain. There is evidence that the domain has diguanylate cyclase activity [1][3]. Several proteins carrying this domain also carry domains with functions relating to environmental sensing. These include PleD, a response regulator protein involved in the swarmer-to-stalked cell transition in Caulobacter crescentus[2], and FixL, a heme-containing oxygen sensor protein.

Date:

2021-04-27