Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication

Lori, Christian; Ozaki, Shogo; Steiner, Samuel; Böhm, Raphael; Abel, Sören; Dubey, Badri N.; Schirmer, Tilman; Hiller, Sebastian; Jenal, Urs

doi:10.1038/nature14473

Cited by 172 publications

(218 citation statements)

References 46 publications

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“…Other mechanisms for producing asymmetry in polar localization are signaling through phosphorylation and c-di-GMP binding. Five of the six PopZ binding proteins identified in this study are affected, either directly or indirectly, by one or both of these signaling mechanisms (31,32). An example is the switch from monopolar to bipolar distribution in CpdR mutants that cannot be phosphorylated (33).…”

Section: Discussionmentioning

confidence: 99%

Caulobacter PopZ forms an intrinsically disordered hub in organizing bacterial cell poles

Holmes

Follett

Hai-bi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

158

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Despite their relative simplicity, bacteria have complex anatomy at the subcellular level. At the cell poles of Caulobacter crescentus, a 177-amino acid (aa) protein called PopZ self-assembles into 3D polymeric superstructures. Remarkably, we find that this assemblage interacts directly with at least eight different proteins, which are involved in cell cycle regulation and chromosome segregation. The binding determinants within PopZ include 24 aa at the N terminus, a 32-aa region near the C-terminal homo-oligomeric assembly domain, and portions of an intervening linker region. Together, the N-terminal 133 aa of PopZ are sufficient for interacting with all binding partners, even in the absence of homooligomeric assembly. Structural analysis of this region revealed that it is intrinsically disordered, similar to p53 and other hub proteins that organize complex signaling networks in eukaryotic cells. Through live-cell photobleaching, we find rapid binding kinetics between PopZ and its partners, suggesting many pole-localized proteins become concentrated at cell poles through rapid cycles of binding and unbinding within the PopZ scaffold. We conclude that some bacteria, similar to their eukaryotic counterparts, use intrinsically disordered hub proteins for network assembly and subcellular organization.PopZ | intrinsically disordered protein | bacteria | Caulobacter | hub protein

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Section: Discussionmentioning

confidence: 99%

Caulobacter PopZ forms an intrinsically disordered hub in organizing bacterial cell poles

Holmes

Follett

Hai-bi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

158

View full text Add to dashboard Cite

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“…There are numerous unanswered questions concerning the nature of the c-di-GMP regulatory system and the ecological factors shaping its evolution (Hengge, 2009;Srivastava and Waters, 2012;Kulasekara et al, 2013;Romling et al, 2013;Lori et al, 2015). A particularly pressing issue concerns the ecological significance of adhesive traits in environments where expression of these traits is subject to gene regulation (Gal et al, 2003;Giddens et al, 2007), as opposed to overexpression upon mutational activation, which is the norm in laboratory models of evolution.…”

Section: Evolutionary Convergencementioning

confidence: 99%

Evolutionary convergence in experimental Pseudomonas populations

2016

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Model microbial systems provide opportunity to understand the genetic bases of ecological traits, their evolution, regulation and fitness contributions. Experimental populations of Pseudomonas fluorescens rapidly diverge in spatially structured microcosms producing a range of surfacecolonising forms. Despite divergent molecular routes, wrinkly spreader (WS) niche specialist types overproduce a cellulosic polymer allowing mat formation at the air-liquid interface and access to oxygen. Given the range of ways by which cells can form mats, such phenotypic parallelism is unexpected. We deleted the cellulose-encoding genes from the ancestral genotype and asked whether this mutant could converge on an alternate phenotypic solution. Two new traits were discovered. The first involved an exopolysaccharide encoded by pgaABCD that functions as cell-cell glue similar to cellulose. The second involved an activator of an amidase (nlpD) that when defective causes cell chaining. Both types form mats, but were less fit in competition with cellulose-based WS types. Surprisingly, diguanylate cyclases linked to cellulose overexpression underpinned evolution of poly-beta-1,6-N-acetyl-D-glucosamine (PGA)-based mats. This prompted genetic analyses of the relationships between the diguanylate cyclases WspR, AwsR and MwsR, and both cellulose and PGA. Our results suggest that c-di-GMP regulatory networks may have been shaped by evolution to accommodate loss and gain of exopolysaccharide modules facilitating adaptation to new environments.

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“…An efficient and selective in vivo fluorescent biosensor assay enabled the discovery of this previously unidentified activity, highlighting RNA-based biosensors as an attractive technology platform for enzyme screening. Alternative screening strategies such as fractionation (15,16), in vitro enzyme screening (41), or a phenotype-based assay in the native organism (42) are relatively more time and resource intensive. The in vivo biosensor assay is particularly useful for signal transduction enzymes that are activated by dimerization, because this can be mimicked by overexpression in a heterologous host.…”

Section: Whereas Previous Ggdef Enzymes Were Uniformly Assigned As Dgmentioning

confidence: 99%

Hybrid promiscuous (Hypr) GGDEF enzymes produce cyclic AMP-GMP (3′, 3′-cGAMP)

Hallberg

Wang

Wright

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

104

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Over 30 years ago, GGDEF domain-containing enzymes were shown to be diguanylate cyclases that produce cyclic di-GMP (cdiG), a second messenger that modulates the key bacterial lifestyle transition from a motile to sessile biofilm-forming state. Since then, the ubiquity of genes encoding GGDEF proteins in bacterial genomes has established the dominance of cdiG signaling in bacteria. However, the observation that proteobacteria encode a large number of GGDEF proteins, nearing 1% of coding sequences in some cases, raises the question of why bacteria need so many GGDEF enzymes. In this study, we reveal that a subfamily of GGDEF enzymes synthesizes the asymmetric signaling molecule cyclic AMP-GMP (cAG or 3′, 3′-cGAMP). This discovery is unexpected because GGDEF enzymes function as symmetric homodimers, with each monomer binding to one substrate NTP. Detailed analysis of the enzyme from Geobacter sulfurreducens showed it is a dinucleotide cyclase capable of switching the major cyclic dinucleotide (CDN) produced based on ATP-to-GTP ratios. We then establish through bioinformatics and activity assays that hybrid CDN-producing and promiscuous substrate-binding (Hypr) GGDEF enzymes are found in other deltaproteobacteria. Finally, we validated the predictive power of our analysis by showing that cAG is present in surface-grown Myxococcus xanthus. This study reveals that GGDEF enzymes make alternative cyclic dinucleotides to cdiG and expands the role of this widely distributed enzyme family to include regulation of cAG signaling.bacterial signaling | surface sensing | second messengers | cyclic dinucleotides | fluorescent biosensor

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Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication

Cited by 172 publications

References 46 publications

Caulobacter PopZ forms an intrinsically disordered hub in organizing bacterial cell poles

Caulobacter PopZ forms an intrinsically disordered hub in organizing bacterial cell poles

Evolutionary convergence in experimental Pseudomonas populations

Hybrid promiscuous (Hypr) GGDEF enzymes produce cyclic AMP-GMP (3′, 3′-cGAMP)

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