title: Simulations of stressosome activation emphasize allosteric interactions between RsbR and RsbT.
abstract: BACKGROUND
  The stressosome is a bacterial signalling complex that responds to environmental changes by initiating a protein partner switching cascade, which leads to the release of the alternative sigma factor, σB. Stress perception increases the phosphorylation of the stressosome sensor protein, RsbR, and the scaffold protein, RsbS, by the protein kinase, RsbT. Subsequent dissociation of RsbT from the stressosome activates the σB cascade. However, the sequence of physical events that occur in the stressosome during signal transduction is insufficiently understood.
  
  
  RESULTS
  Here, we use computational modelling to correlate the structure of the stressosome with the efficiency of the phosphorylation reactions that occur upon activation by stress. In our model, the phosphorylation of any stressosome protein is dependent upon its nearest neighbours and their phosphorylation status. We compare different hypotheses about stressosome activation and find that only the model representing the allosteric activation of the kinase RsbT, by phosphorylated RsbR, qualitatively reproduces the experimental data.
  
  
  CONCLUSIONS
  Our simulations and the associated analysis of published data support the following hypotheses: (i) a simple Boolean model is capable of reproducing stressosome dynamics, (ii) different stressors induce identical stressosome activation patterns, and we also confirm that (i) phosphorylated RsbR activates RsbT, and (ii) the main purpose of RsbX is to dephosphorylate RsbS-P.
authors: Department of Systems Biology & Bioinformatics, Institute of Computer Science, University of Rostock, 18051, Rostock, Germany. Ulf.liebal@uni-rostock.de
authors: Ulf W
authors: UW
authors: Liebal
authors: Thomas
authors: T
authors: Millat
authors: Jon
authors: J
authors: Marles-Wright
authors: Richard J
authors: RJ
authors: Lewis
authors: Olaf
authors: O
authors: Wolkenhauer
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012808:Sigma Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D010750:Phosphoproteins; C119218:RsbR protein, Bacillus subtilis; C079011:SigB protein, Bacteria; D012808:Sigma Factor; C119219:RsbT protein, Bacillus subtilis; D017346:Protein Serine-Threonine Kinases