Intrinsic Thermal Sensing Controls Proteolysis of Yersinia Virulence Regulator RovA

PLoS Pathogens

Martin Weichert¹  Matthias Bujara¹  Petra Dersch¹  Wiebke Opitz²  Ariane Zimmermann²  Ann Kathrin Heroven²  Katharina Herbst² 

[1] Abteilung Molekulare Infektionsbiologie, Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany;Institut für Mikrobiologie, Technische Universität Braunschweig, Braunschweig, Germany

关键词: Proteases;    DNA-binding proteins;    Proteolysis;    Yersinia pseudotuberculosis;    Regulator genes;    Yersinia;    Plasmid construction;    Virulence factors;   

DOI  :  10.1371/journal.ppat.1000435

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Pathogens, which alternate between environmental reservoirs and a mammalian host, frequently use thermal sensing devices to adjust virulence gene expression. Here, we identify the Yersinia virulence regulator RovA as a protein thermometer. Thermal shifts encountered upon host entry lead to a reversible conformational change of the autoactivator, which reduces its DNA-binding functions and renders it more susceptible for proteolysis. Cooperative binding of RovA to its target promoters is significantly reduced at 37°C, indicating that temperature control of rovA transcription is primarily based on the autoregulatory loop. Thermally induced reduction of DNA-binding is accompanied by an enhanced degradation of RovA, primarily by the Lon protease. This process is also subject to growth phase control. Studies with modified/chimeric RovA proteins indicate that amino acid residues in the vicinity of the central DNA-binding domain are important for proteolytic susceptibility. Our results establish RovA as an intrinsic temperature-sensing protein in which thermally induced conformational changes interfere with DNA-binding capacity, and secondarily render RovA susceptible to proteolytic degradation.

【 授权许可】

CC BY