title: Regulated protein aggregation: a mechanism to control the activity of the ClpXP adaptor protein YjbH.
abstract: Bacteria use stress response pathways to activate diverse target genes to react to a variety of stresses. The Bacillus subtilis Spx protein is a global transcriptional regulator that controls expression of more than 140 genes and operons in response to thiol-specific oxidative stress. Under nonstress conditions the concentration of Spx is kept low by proteolysis catalyzed by the ClpXP complex. Spx protein levels increase in response to disulfide stress and decrease when the cells cope with the stress. The cytosolic adaptor protein YjbH is required to target Spx for efficient proteolysis by ClpXP. We demonstrate that YjbH aggregates in response to disulfide stress, that is, the YjbH protein is soluble under nonstressed conditions and destabilized during stress leading to aggregation. Stress conditions (heat and ethanol) that cause severe perturbations in protein stability/folding also induced aggregation of YjbH and led to induction of Spx. By heterologous expression of a less aggregation prone YjbH homolog Spx induction was abolished. Thus we show that moderation of YjbH solubility is an important mechanism of signal transduction and represents a new mechanism of controlling the activity of adaptor proteins.
authors.affiliation: Department of Biology, Lund University, Sölvegatan 35, Lund, SE-223 62, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Engman
authors.forename: Claes
authors.initials: C
authors.lastname: von Wachenfeldt
mesh_terms: D001412:Bacillus subtilis / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D004220:Disulfides / Q000378:metabolism*; D049071:Endopeptidase Clp / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D018384:Oxidative Stress; D066329:Protein Aggregates; D055550:Protein Stability; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D004220:Disulfides; D066329:Protein Aggregates; D049071:Endopeptidase Clp