Insights into the co-evolution of regulator/operator selectivity among MerR transcription factors

HUMBERT, M. V.; CHECA, S. K.; SONCINI, F. C.

Potrero de los Funes, San Luis

Congreso; XLVII Reunión Anual; 2011

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Metal ions are essential cellular constituents but they can be toxic at high concentration. In Salmonella, two paralog metal sensors of the MerR family, CueR and GolS, direct the response to Cu, Au and Ag ions by inducing the expression of different set of transporters. Previously, we demonstrated that cross-activation between CueR- and GolS-controlled promoters is prevented in two ways: the presence of distinctive bases at the centre of the operator sequences that confer selectivity towards their innate regulator, and a tight control of the cytoplasmic concentration of each transcription factor. Here, we evaluated the role of the domain and the amino acid residues that privilege binding to CueR and GolS target operators. The interaction of each mutant regulator with target promoters from both regulons was evaluated both in vivo and in vitro. Our studies indicate that the selective operator activation relies on the á2-helix, in particular the residue at position 16 within this helix. Furthermore, we show that all GolS xenologes harbour an invariant M residue at this position while T, A or S, but not M, are present in CueR-like proteins. The co-evolution of distinctive features in both the transcription factor and its target promoters guarantee selective recognition and a proper response to metals.