title: CtsR inactivation during thiol-specific stress in low GC, Gram+ bacteria.
abstract: CtsR, the global heat shock repressor in low GC, Gram+ bacteria, regulates a crucial subset of genes involved in protein quality control. CtsR de-repression occurs not only during heat stress but also during a variety of other environmental stresses, most notably thiol-specific oxidative stress. Here we report that McsA acts as a molecular redox switch that regulates CtsR de-repression via the activation of McsB. Once critical thiols of McsA become oxidized, the strong interaction between McsA and McsB is interrupted and free McsB is no longer inhibited by McsA, resulting in the inactivation of CtsR. This mechanism differs significantly from inactivation of CtsR during heat stress demonstrating a dual activity control of CtsR. Moreover, we show that in those low GC, Gram+ bacteria, which lack the McsA/McsB complex, the Zn finger protein ClpE is able to sense and respond to oxidative stress, also resulting in CtsR inactivation.
authors.affiliation: Institute of Microbiology, Ernst-Moritz-Arndt-University Greifswald, F.-L.-Jahnstr. 15, D-17487 Greifswald, Germany.
authors.forename: Alexander K W
authors.initials: AK
authors.lastname: Elsholz
authors.forename: Kristina
authors.initials: K
authors.lastname: Hempel
authors.forename: Dierk-Christoph
authors.initials: DC
authors.lastname: Pöther
authors.forename: Dörte
authors.initials: D
authors.lastname: Becher
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
authors.forename: Ulf
authors.initials: U
authors.lastname: Gerth
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001482:Base Composition / Q000235:genetics*; D004220:Disulfides / Q000494:pharmacology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000187:drug effects; D007700:Kinetics; D008954:Models, Biological; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D001426:Bacterial Proteins; C118338:CtsR protein, bacteria; D004220:Disulfides; D006360:Heat-Shock Proteins; C423321:McsA protein, Bacillus subtilis; D012097:Repressor Proteins; D013438:Sulfhydryl Compounds; D011494:Protein Kinases; C423322:McsB protein, Bacillus subtilis; D000251:Adenosine Triphosphatases; C118340:ClpE protein, bacteria