Die NreA/NreB Sensoren von Staphylococcus carnosus: Ein Sensorkomplex zur koordinierten Erkennung von Sauerstoff und Nitrat
Zusammenfassung der Projektergebnisse
The advent of O2 about 2.5 billion years ago forced microbes to adapt metabolism and to find mechanisms for O2sensing. Sensing of O2 by [4Fe-4S]2+ to [2Fe-2S]2+ cluster conversion represents an ancient mechanism which is used by sensors FNREc (Escherichia coli), FNRBs (Bacillus subtilis), NreBSa (Staphylococcus aureus), and WhiB3Mt (Mycobacterium tuberculosis). The phylogenetic relationship of the sensors was investigated. FNREc homologs are restricted to the proteobacteria and few representtatives from other phyla. Homologs of FNRBs and NreBSa are located within the Bacilli, of WhiB3 in the Actinobacteria. The Archaea contain no homologs. The data suggest independent development of the sensors in phyla that were already present during advent of O2, and limited distribution by lateral gene transfer. Chemistry of the [4Fe-4S] and [2Fe-2S] clusters is in agreement with their independent acquisition to different proteins. Despite the same cluster chemistry, the sensors produce different forms of signal output. The homologs of FNREc and NreBSa comprise variants with regard to the four Cys ligands that ligate the cluster (3Cys-, 2Cys-, 1Cys- and 0Cys-variants). It is suggested that the variants derive from lateral gene transfer and gained then other functions. The NreB-NreC two-component system requires the nitrate binding protein NreA for full activity, and NreA-NreB-NreC form a tripartite unit for nitrate/O2 cosensing. O2 regulates the basic activity of the NreB sensor kinase, using an O2-responsive [4Fe-4S]2+ cluster. The presence of nitrate is sensed by NreA, and the NreA-Nitrate complex stimulates autokinase activity of NreB. The present study shows that a DxxxQ motif in NreB represents a phosphatase site for NreC-P dephosphorylation. Unexpectedly, NreA controls NreB function by switching NreB from the kinase to the phosphatase state. Binding of NreA (nitrate bound state) and NreA (nitrate deficient state) convert NreB from the kinase state (NreB autophosphorylation, i.e. high activity) to the phosphatase state (dephosphorylation and inactivation of NreC-P).
Projektbezogene Publikationen (Auswahl)
- (2018) Origin and phylogenetic relationships of [4Fe-4S]-containing O2 sensors of bacteria. Env Microbiol 20: 4567-4586. doi: 10.1111/1462-2920
Barth C, Weiss M, Roettger M, Martin W, Unden G
(Siehe online unter https://doi.org/10.1111/1462-2920.14411)