title: The atypical two-component sensor kinase Lpl0330 from Legionella pneumophila controls the bifunctional diguanylate cyclase-phosphodiesterase Lpl0329 to modulate bis-(3'-5')-cyclic dimeric GMP synthesis.
abstract: A significant part of bacterial two-component system response regulators contains effector domains predicted to be involved in metabolism of bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), a second messenger that plays a key role in many physiological processes. The intracellular level of c-di-GMP is controlled by diguanylate cyclase and phosphodiesterases activities associated with GGDEF and EAL domains, respectively. The Legionella pneumophila Lens genome displays 22 GGDEF/EAL domain-encoding genes. One of them, lpl0329, encodes a protein containing a two-component system receiver domain and both GGDEF and EAL domains. Here, we demonstrated that the GGDEF and EAL domains of Lpl0329 are both functional and lead to simultaneous synthesis and hydrolysis of c-di-GMP. Moreover, these two opposite activities are finely regulated by Lpl0329 phosphorylation due to the atypical histidine kinase Lpl0330. Indeed, Lpl0330 was found to autophosphorylate on a histidine residue in an atypical H box, which is conserved in various bacteria species and thus defines a new histidine kinase subfamily. Lpl0330 also catalyzes the phosphotransferase to Lpl0329, which results in a diguanylate cyclase activity decrease whereas phosphodiesterase activity remains efficient. Altogether, these data present (i) a new histidine kinase subfamily based on the conservation of an original H box that we named HGN H box, and (ii) the first example of a bifunctional enzyme that modulates synthesis and turnover of c-di-GMP in response to phosphorylation of its receiver domain.
authors.affiliation: Université de Lyon, Université Lyon 1, CNRS UMR5240 Microbiologie, Adaptation et Pathogénie, 69622 Villeurbanne, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Levet-Paulo
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lazzaroni
authors.forename: Christophe
authors.initials: C
authors.lastname: Gilbert
authors.forename: Danièle
authors.initials: D
authors.lastname: Atlan
authors.forename: Patricia
authors.initials: P
authors.lastname: Doublet
authors.forename: Anne
authors.initials: A
authors.lastname: Vianney
mesh_terms: D001426:Bacterial Proteins; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000096:biosynthesis; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005798:Genes, Bacterial; D016952:Legionella pneumophila / Q000201:enzymology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D019761:Phosphorus-Oxygen Lyases / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D011494:Protein Kinases; D010727:Phosphoric Diester Hydrolases; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP