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Science 5 June 2009:
Vol. 324. no. 5932, pp. 1323 - 1327
DOI: 10.1126/science.1170088

Reports

McsB Is a Protein Arginine Kinase That Phosphorylates and Inhibits the Heat-Shock Regulator CtsR

Jakob Fuhrmann,1,* Andreas Schmidt,2,* Silvia Spiess,3 Anita Lehner,1 Kürsad Turgay,4 Karl Mechtler,1,5 Emmanuelle Charpentier,3,6 Tim Clausen1,{dagger}

All living organisms face a variety of environmental stresses that cause the misfolding and aggregation of proteins. To eliminate damaged proteins, cells developed highly efficient stress response and protein quality control systems. We performed a biochemical and structural analysis of the bacterial CtsR/McsB stress response. The crystal structure of the CtsR repressor, in complex with DNA, pinpointed key residues important for high-affinity binding to the promoter regions of heat-shock genes. Moreover, biochemical characterization of McsB revealed that McsB specifically phosphorylates arginine residues in the DNA binding domain of CtsR, thereby impairing its function as a repressor of stress response genes. Identification of the CtsR/McsB arginine phospho-switch expands the repertoire of possible protein modifications involved in prokaryotic and eukaryotic transcriptional regulation.

1 Research Institute of Molecular Pathology, Dr. Bohrgasse 7, A-1030 Vienna, Austria.
2 Christian Doppler Laboratory for Proteome Analysis, University of Vienna, Dr. Bohrgasse 3, A-1030 Vienna, Austria.
3 Max F. Perutz Laboratories, University of Vienna, Dr. Bohrgasse 9, A-1030 Vienna, Austria.
4 Institute for Biology–Microbiology, Freie Universität Berlin, Königin-Luisé-Str. 12-16, 14195 Berlin, Germany.
5 Institute for Molecular Biotechnology–IMBA, Dr. Bohrgasse 3, A-1030 Vienna, Austria.
6 The Laboratory for Molecular Infection Medicine Sweden, Umeå University, S-90187 Umeå, Sweden.

* These authors contributed equally to the work.

{dagger} To whom correspondence should be addressed. E-mail: clausen{at}imp.univie.ac.at

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A New Mechanism of Phosphoregulation in Signal Transduction Pathways.
K. Jung and H. Jung (2009)
Science Signaling 2, pe71
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