Structural basis for intrinsic thermosensing by the master virulence regulator RovA of Yersinia.
Title | Structural basis for intrinsic thermosensing by the master virulence regulator RovA of Yersinia. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Quade, N, Mendonca, C, Herbst, K, Heroven, AK, Ritter, C, Heinz, DW, Dersch, P |
Journal | J Biol Chem |
Date Published | 2012 Aug 30 |
ISSN | 1083-351X |
Abstract | Pathogens often rely on thermosensing to adjust virulence gene expression. In yersiniae, important virulence-associated traits are under the control of the master regulator RovA which uses an in-built thermosensor to control its activity. Thermal upshifts encountered upon host entry induce conformational changes of the RovA dimer that attenuate DNA-binding and render the protein more susceptible to proteolysis. Here, we report the crystal structure of RovA in the free and DNA-bound form and provide evidence that thermo-induced loss of RovA activity is mainly promoted by a thermosensing loop in the dimerization domain and residues in the adjacent C-terminal helix. These determinants allow partial unfolding of the regulator upon an upshift to 37°C. This structural distortion is transmitted to the flexible DNA-binding domain of RovA. RovA mainly contacts the DNA backbone in a low affinity-binding mode which allows the immediate release of RovA from its operator sites. We also show that SlyA, a close homologue of RovA from Salmonella with a very similar structure, is not a thermosensor and remains active and stable at 37°C. Strikingly, changes in only three amino acids, reflecting evolutionary replacements in SlyA, result in a complete loss of the thermosensing properties of RovA and prevent degradation. In conclusion, only minor alterations can transform a thermotolerant regulator into a thermosensor that allows adjustment of virulence and fitness determinants to their thermal environment. |
DOI | 10.1074/jbc.M112.379156 |
Alternate Journal | J. Biol. Chem. |