Title
Promiscuity of response regulators for thioredoxin steers bacterial virulence
Author
Ju-Sim Kim, Alexandra Born, James Karl A. Till, Lin Liu, Sashi Kant, Morkos A. Henen, Beat Vögeli & Andrés Vázquez-Torres
Year
2022
Journal
Nature communications
Abstract
The exquisite specificity between a sensor kinase and its cognate response regulator ensures faithful partner selectivity within two-component pairs concurrently firing in a single bacterium, minimizing crosstalk with other members of this conserved family of paralogous proteins. We show that conserved hydrophobic and charged residues on the surface of thioredoxin serve as a docking station for structurally diverse response regulators. Using the OmpR protein, we identify residues in the flexible linker and the C-terminal β-hairpin that enable associations of this archetypical response regulator with thioredoxin, but are dispensable for interactions of this transcription factor to its cognate sensor kinase EnvZ, DNA or RNA polymerase. Here we show that the promiscuous interactions of response regulators with thioredoxin foster the flow of information through otherwise highly dedicated two-component signaling systems, thereby enabling both the transcription of Salmonella pathogenicity island-2 genes as well as growth of this intracellular bacterium in macrophages and mice.
Full Article
Instrument
J-815
Keywords
thioredoxin, DNA, RNA, C-terminal