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ReportsMcsB Is a Protein Arginine Kinase That Phosphorylates and Inhibits the Heat-Shock Regulator CtsR ad Turgay,4![]()
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.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)