Figure 1.

LiaFSR signaling pathway. In the absence of cell membrane-acting antibiotics, the three-component regulatory system, LiaFSR, is turned ‘OFF’ by the negative interaction of LiaF with LiaS. LiaS responds to membrane stress by phosphorylation of LiaR leading to downstream changes in the transcription of several operons to affect membrane homeostasis. E. faecalis LiaR is present largely as a dimer at physiologically relevant concentrations. Phosphorylation, or mutation to a constitutively active analog like LiaR^D191N, induces changes in the conformation of the receiver domain leading to release of DNA binding domain and promoting a self-dimerization event to form an active tetramer able to bind extended DNA sequences. Abbreviations: RD, receiver domain; DBD, DNA binding domain.