Summary information and primary citation
- PDB-id
- 4aik; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- transcription
- Method
- X-ray (1.85 Å)
- Summary
- Crystal structure of rova from yersinia in complex with an invasin promoter fragment
- Reference
- Quade N, Mendonca C, Herbst K, Heroven AK, Ritter C, Heinz DW, Dersch P (2012): "Structural Basis for Intrinsic Thermosensing by the Master Virulence Regulator Rova of Yersinia." J.Biol.Chem., 287, 35796. doi: 10.1074/JBC.M112.379156.
- 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.
