Fig. 1

Modularity of two-component signaling circuits (TCSs). When the sensor domain of a canonical SHK perceives stimulus, communication occurs across the membrane (black line) resulting in increased kinase activity of the catalytic ATPase (CA) domain. This enhances phosphorylation of the conserved histidyl residue within the domain responsible for dimerization and histidylphosphotransfer (DHp). These nascent phosphoryl groups are subsequently transferred to an aspartyl residue within the receiver domain of the RR, which usually increases the DNA-binding activity of the output domain leading to transcription of a group of genes, known as a regulon, related to the cognate stimulus [1]. Aromatic tuning, or moving aromatic residues (red box) at the cytoplasmic end of the transmembrane (TM) domain, facilitates stimulus-independent modulation of signaling circuits by mimicking the presence of cognate stimulus and thus altering SHK output, and in turn, transcription of the associated regulon