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dc.contributor.authorQuade, Nick
dc.contributor.authorMendonca, Chriselle
dc.contributor.authorHerbst, Katharina
dc.contributor.authorHeroven, Ann Kathrin
dc.contributor.authorRitter, Christiane
dc.contributor.authorHeinz, Dirk W
dc.contributor.authorDersch, Petra
dc.date.accessioned2012-11-16T14:53:59Zen
dc.date.available2012-11-16T14:53:59Zen
dc.date.issued2012-10-19en
dc.identifier.citationStructural Basis for Intrinsic Thermosensing by the Master Virulence Regulator RovA of Yersinia. 2012, 287 (43):35796-803 J. Biol. Chem.en_GB
dc.identifier.issn1083-351Xen
dc.identifier.pmid22936808en
dc.identifier.doi10.1074/jbc.M112.379156en
dc.identifier.urihttp://hdl.handle.net/10033/252471en
dc.description.abstractPathogens 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 a built-in thermosensor to control its activity. Thermal upshifts encountered upon host entry induce conformational changes in 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 forms and provide evidence that thermo-induced loss of RovA activity is promoted mainly 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 contacts mainly 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 homolog 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.
dc.language.isoenen
dc.rightsArchived with thanks to The Journal of biological chemistryen_GB
dc.titleStructural Basis for Intrinsic Thermosensing by the Master Virulence Regulator RovA of Yersinia.en
dc.typeArticleen
dc.contributor.departmentFrom the Departments of Molecular Structural Biology and.en_GB
dc.identifier.journalThe Journal of biological chemistryen_GB
refterms.dateFOA2013-10-15T00:00:00Z
html.description.abstractPathogens 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 a built-in thermosensor to control its activity. Thermal upshifts encountered upon host entry induce conformational changes in 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 forms and provide evidence that thermo-induced loss of RovA activity is promoted mainly 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 contacts mainly 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 homolog 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.


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