2.50
HDL Handle:
http://hdl.handle.net/10033/252471
Title:
Structural Basis for Intrinsic Thermosensing by the Master Virulence Regulator RovA of Yersinia.
Authors:
Quade, Nick; Mendonca, Chriselle; Herbst, Katharina; Heroven, Ann Kathrin; Ritter, Christiane; Heinz, Dirk W; Dersch, Petra
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 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.
Affiliation:
From the Departments of Molecular Structural Biology and.
Citation:
Structural Basis for Intrinsic Thermosensing by the Master Virulence Regulator RovA of Yersinia. 2012, 287 (43):35796-803 J. Biol. Chem.
Journal:
The Journal of biological chemistry
Issue Date:
19-Oct-2012
URI:
http://hdl.handle.net/10033/252471
DOI:
10.1074/jbc.M112.379156
PubMed ID:
22936808
Type:
Article
Language:
en
ISSN:
1083-351X
Appears in Collections:
Publications of Molekulare Infektionsbiologie(MIBI)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorQuade, Nicken_GB
dc.contributor.authorMendonca, Chriselleen_GB
dc.contributor.authorHerbst, Katharinaen_GB
dc.contributor.authorHeroven, Ann Kathrinen_GB
dc.contributor.authorRitter, Christianeen_GB
dc.contributor.authorHeinz, Dirk Wen_GB
dc.contributor.authorDersch, Petraen_GB
dc.date.accessioned2012-11-16T14:53:59Z-
dc.date.available2012-11-16T14:53:59Z-
dc.date.issued2012-10-19-
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.issn1083-351X-
dc.identifier.pmid22936808-
dc.identifier.doi10.1074/jbc.M112.379156-
dc.identifier.urihttp://hdl.handle.net/10033/252471-
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.en_GB
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

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