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Query: UMLS:C1832526 (PCC)
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Computational analysis of gene structures in the genome of Anabaena sp. PCC 7120 revealed the presence of a large number of genes encoding proteins with multiple functional domains. This was most evident in the genes for signal transduction pathway and the related systems. Comparison of the putative amino acid sequences of the gene products with those in the Pfam database indicated that and PAS domains which may be involved in signal recognition were extremely abundant in Anabaena: 87 GAF domains in 62 ORFs and 140 PAS domains in 59 ORFs. As for the two-component signal transduction system, 73, 53, and 77 genes for simple sensory His kinases, hybrid His kinases and simple response regulators, respectively, many of which contained additional domains of diverse functions, were presumptively assigned. A total of 52 ORFs encoding putative Hanks-type Ser/Thr protein kinases with various domains such as WD-repeat, GAF and His kinase domains, as well as genes for presumptive protein phosphatases, were also identified. In addition, genes for putative transcription factors and for proteins in the cAMP signal transduction system harbored complex gene structures with multiple domains.
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PMID:Characterization of genes encoding multi-domain proteins in the genome of the filamentous nitrogen-fixing Cyanobacterium anabaena sp. strain PCC 7120. 1185 27

The gene cyaB1 from the cyanobacterium Anabaena sp. PCC 7120 codes for a protein consisting of two N-terminal GAF domains (GAF-A and GAF-B), a PAS domain and a class III adenylyl cyclase catalytic domain. The catalytic domain is active as a homodimer, as demonstrated by reconstitution from complementary inactive point mutants. The specific activity of the holoenyzme increased exponentially with time because the product cAMP activated dose dependently and nucleotide specifically (half-maximally at 1 microM), identifying cAMP as a novel GAF domain ligand. Using point mutants of either the GAF-A or GAF-B domain revealed that cAMP activated via the GAF-B domain. We replaced the cyanobacterial GAF domain ensemble in cyaB1 with the tandem GAF-A/GAF-B assemblage from the rat cGMP-stimulated phosphodiesterase type 2, and converted cyaB1 to a cGMP-stimulated adenylyl cyclase. This demonstrated the functional conservation of the GAF domain ensemble since the divergence of bacterial and eukaryotic lineages >2 billion years ago. In cyanobacteria, cyaB1 may act as a cAMP switch to stabilize committed developmental decisions.
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PMID:A GAF-domain-regulated adenylyl cyclase from Anabaena is a self-activating cAMP switch. 1211 May 80

We recently described the cikA (circadian input kinase A) gene, whose product supplies environmental information to the circadian oscillator in the cyanobacterium Synechococcus elongatus PCC 7942. CikA possesses three distinct domains: a GAF, a histidine protein kinase (HPK), and a receiver domain similar to those of the response regulator family. To determine how CikA functions in providing circadian input, we constructed modified alleles to tag and truncate the protein, allowing analysis of each domain individually. CikA covalently bound bilin chromophores in vitro, even though it lacks the expected ligand residues, and the GAF domain influenced but did not entirely account for this function. Full-length CikA and truncated variants that carry the HPK domain showed autophosphorylation activity. Deletion of the GAF domain or the N-terminal region adjacent to GAF dramatically reduced autophosphorylation, whereas elimination of the receiver domain increased activity 10-fold. Assays to test phosphorelay from the HPK to the cryptic receiver domain, which lacks the conserved aspartyl residue that serves as a phosphoryl acceptor in response regulators, were negative. We propose that the cryptic receiver is a regulatory domain that interacts with an unknown protein partner to modulate the autokinase activity of CikA but does not work as bona fide receiver domain in a phosphorelay.
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PMID:Biochemical properties of CikA, an unusual phytochrome-like histidine protein kinase that resets the circadian clock in Synechococcus elongatus PCC 7942. 1262 98

The gene, pixJ1 (formerly pisJ1), is predicted to encode a phytochrome-like photoreceptor that is essential for positive phototaxis in the unicellular cyanobacterium Synechocystis sp. PCC 6803 [Yoshihara et al. (2000) Plant Cell Physiol. 41: 1299]. The PixJ1 protein was overexpressed as a fusion with a poly-histidine tag (His-PixJ1) and isolated from Synechocystis cells. A zinc-fluorescence assay suggested that a linear tetrapyrrole was covalently attached to the His-PixJ1 protein as a chromophore. His-PixJ1 showed novel photoreversible conversion between a blue light-absorbing form (Pb, lambdaAmax=425-435 nm) and a green light-absorbing form (Pg, lambdaAmax=535 nm). Dark incubation led Pg to revert to Pb, indicative of stability of the Pb form in darkness. Red or far-red light irradiation, which is effective for photochemical conversion of the known phytochromes, produced no change in the spectra of Pb and Pg forms. Site-directed mutagenesis revealed that a Cys-His motif in the second GAF domain of PixJ1 is responsible for binding of the chromophore. Possible chromophore species are discussed with regard to the novel photoconversion spectrum.
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PMID:Cyanobacterial phytochrome-like PixJ1 holoprotein shows novel reversible photoconversion between blue- and green-absorbing forms. 1565 92

PixJ1, a photoreceptor in the unicellular cyanobacterium Synechocystis sp. PCC 6803, mediates positive phototactic motility and contains two GAF domains, the latter of which binds a bilin chromophore. Full-length PixJ1 expressed and purified from Synechocystis showed unique reversible photoconversion between a blue light-absorbing (Pb) form and a green light-absorbing (Pg) form (1) in contrast to the reversible phototransformation between the red light-absorbing form and far-red light-absorbing form of the other GAF-containing photoreceptors such as plant or bacterial phytochromes. To clarify the origin of the blue-shifted photoconversion, we tried to reconstitute this blue-green reversible phototransformation by synthesizing the second GAF domain in Escherichia coli transformed with genes for biosynthesis of four different bilins, biliverdin (BV), bilirubin (BR), phycocyanobilin (PCB), and phycocyanorubin (PCR), as final products. The three expression systems, the BR system being the exception, produced a GAF polypeptide with a covalently bound bilin. The GAF polypeptide from the BV-synthesizing system exhibited an irreversible photoconversion, while that from the PCB-synthesizing system revealed photoconversion between Pb and Pg almost identical to that of the full-length PixJ1, indicating that PCB is responsible for the blue-green reversible photoconversion. Furthermore, the GAF polypeptide from the PCR-producing system exhibited almost the same reversible spectral change, possibly coming from the PCB accumulated in the PCR-biosynthetic pathway. Mass spectrometry (MS) of the main tryptic chromopeptide revealed that the chromophore binds to a 21-amino acid peptide that contains a cysteine-histidine motif for phytochrome chromophore binding and that an ion signal can be assigned to desorbed PCB. The absorption spectra of the denatured GAF polypeptide suggested that PCB is attached to the protein moiety in a twisted conformation that disrupts the pi-electron conjugation between the A and B rings, possibly being held in position through a second covalent linkage.
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PMID:Reconstitution of blue-green reversible photoconversion of a cyanobacterial photoreceptor, PixJ1, in phycocyanobilin-producing Escherichia coli. 1653 61

CikA (circadian input kinase) is a component of the cyanobacterial circadian clock that aids in synchronizing the endogenous oscillator with the external environment. cikA mutants of the prokaryotic circadian model organism Synechococcus elongatus PCC 7942 fail to reset the phase of the circadian rhythm of gene expression after an environmental time cue, and also exhibit reduced amplitude and shortened period of circadian oscillation. CikA has histidine protein kinase (HPK) activity that is modulated in vitro by GAF and pseudo-receiver (PsR) domains. Here we show that the PsR domain negatively regulates HPK activity in vivo and also serves as an interaction module to dock CikA at a specific subcellular location. Phenotypes conferred by alleles that encode CikA variants showed that all domains except the featureless N-terminus are required for CikA function. Overexpression of all alleles that encode the PsR domain, whether or not the HPK is functional, caused a dominant arrhythmic phenotype, whereas overexpressed variants that lack PsR did not. Subcellular localization of intact CikA identified a polar focus whereas a variant without PsR showed uniform distribution in the cell, consistent with a model in which PsR mediates interaction with other input pathway components.
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PMID:The pseudo-receiver domain of CikA regulates the cyanobacterial circadian input pathway. 1662 68

A putative photoreceptor gene, TepixJ, of a thermophilic cyanobacterium is homologous to SypixJ1 that mediates positive phototaxis in the unicellular motile cyanobacterium Synechocystis sp. PCC 6803. The putative chromophore-binding GAF domain of TePixJ protein was overexpressed as a fusion with a polyhistidine tag (His-TePixJ_GAF) in Synechocystis cells and isolated to homogeneity. The photoreversible conversion of His-TePixJ_GAF showed peaks at 531, 341 and 266 nm for the green light-absorbing form (Pg form), and peaks at 433 and 287 nm for the blue light-absorbing form (Pb form). At 77K, the Pg form fluoresced at 580 nm, while the Pb form did not emit any fluorescence. Mass spectrometry of the tryptic chromopeptide demonstrated that a phycocyanobilin isomer binds to the conserved cysteine at ring A via a thioether bond. It is established that TePixJ and SyPixJ1 are novel photoreceptors in cyanobacteria ('cyanobacteriochromes') that are similar, but distinct from the phytochromes and bacteriophytochromes.
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PMID:Characterization of cyanobacteriochrome TePixJ from a thermophilic cyanobacterium Thermosynechococcus elongatus strain BP-1. 1688 42

Most organisms maintain a transmembrane sodium gradient for cell function. Despite the importance of Na(+) in physiology, no directly Na(+)-responsive signalling molecules are known. The CyaB1 and CyaB2 adenylyl cyclases of the cyanobacterium Anabaena PCC 7120 are inhibited by Na(+). A D360A mutation in the GAF-B domain of CyaB1 ablated cAMP-mediated autoregulation and Na(+) inhibition. Na(+) bound the isolated GAF domains of CyaB2. cAMP blocked Na(+) binding to GAF domains but Na(+) had no effect on cAMP binding. Na(+) altered GAF domain structure indicating a mechanism of inhibition independent of cAMP binding. DeltacyaB1 and DeltacyaB2 mutant strains did not grow below 0.6 mM Na(+) and DeltacyaB1 cells possessed defects in Na(+)/H(+) antiporter function. Replacement of the CyaB1 GAF domains with those of rat phosphodiesterase type 2 revealed that Na(+) inhibition has been conserved since the eukaryotic/bacterial divergence. CyaB1 and CyaB2 are the first identified directly Na(+)-responsive signalling molecules that function in sodium homeostasis and we propose a subset of GAF domains underpin an evolutionarily conserved Na(+) signalling mechanism.
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PMID:A subset of GAF domains are evolutionarily conserved sodium sensors. 1749 28

Cyclic nucleotide PDEs (phosphodiesterases) regulate cellular levels of cAMP and cGMP by controlling the rate of degradation. Several mammalian PDE isoforms possess N-terminal GAF (found in cGMP PDEs, Anabaena adenylate cyclases and Escherichia coli FhlA; where FhlA is formate hydrogen lyase transcriptional activator) domains that bind cyclic nucleotides. Similarly, the CyaB1 and CyaB2 ACs (adenylate cyclases) of the cyanobacterium Anabaena PCC 7120 bind cAMP through one (CyaB1) or two (CyaB2) N-terminal GAF domains and mediate autoregulation of the AC domain. Sodium inhibits the activity of CyaB1, CyaB2 and mammalian PDE2A in vitro through modulation of GAF domain function. Furthermore, genetic ablation of cyaB1 and cyaB2 gives rise to Anabaena strains defective in homoeostasis at limiting sodium. Sodium regulation of GAF domain function has therefore been conserved since the eukaryotic/prokaryotic divergence. The GAF domain is the first identified protein domain to directly sense and signal changes in environmental sodium.
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PMID:Sodium regulation of GAF domain function. 1795 70

Phytochromes and bacteriophytochromes in plants and some species of bacteria, respectively, are photoreceptors that bind linear tetrapyrroles and can respond to red and far-red light signals in a reversible manner. A related but distinct photoreceptor candidate, CikA (denoted ScCikA), has been reported to reset the circadian clock in the cyanobacterium Synechococcus elongatus PCC 7942 after a dark pulse. However, recent studies have indicated that ScCikA does not function as a photoreceptor but as a redox sensor. Moreover, the Cys residue that covalently ligates the chromophore in phytochromes is not conserved in the ScCikA protein. On the other hand, the CikA homolog in Synechocystis sp. PCC 6803 (Slr1969, denoted SyCikA) retains this conserved Cys residue. In our present study, we have isolated the putative chromophore-binding GAF domain of SyCikA from Synechocystis and phycocyanobilin-producing Escherichia coli. Absorption spectra of both preparations showed two peaks in the UV and violet regions. Irradiation of these proteins with violet light yielded a broad peak in a yellow region at the expense of the peaks in the UV and violet regions. Interestingly, successive irradiation with yellow light did not revert these absorption spectra but a partial dark reversion to the original form was detected. These results suggest that SyCikA may function as a violet light sensor in Synechocystis.
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PMID:Characterization of the photoactive GAF domain of the CikA homolog (SyCikA, Slr1969) of the cyanobacterium Synechocystis sp. PCC 6803. 1884 91


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