Simulations of stressosome activation emphasize allosteric interactions between RsbR and RsbT

BMC Systems Biology

Olaf Wolkenhauer¹  Richard J Lewis³  Jon Marles-Wright⁴  Thomas Millat²  Ulf W Liebal² 

[1] Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, 7600, South Africa;Department of Systems Biology & Bioinformatics, Institute of Computer Science, University of Rostock, 18051, Rostock, Germany;Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, NE2 4HH, UK;Institute of Structural and Molecular Biology, School of Biological Sciences, Edinburgh University, Edinburgh, EH9 3JR, UK

关键词: Stress response;    Cellular automaton;    Signalling;    Stressosome;    Bacillus subtilis;   

Others  :  1143325
DOI  :  10.1186/1752-0509-7-3

 received in 2012-07-23, accepted in 2013-01-07,  发布年份 2013

【 摘 要 】

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, σ^B. 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 σ^B 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.

【 授权许可】

   
2013 Liebal et al.; licensee BioMed Central Ltd.

【 图 表 】

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