Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Arginine / metabolism
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / chemistry
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Crystallography, X-Ray
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DNA, Bacterial / metabolism
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Electrophoretic Mobility Shift Assay
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Gene Expression Regulation, Bacterial
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Geobacillus stearothermophilus / genetics
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Geobacillus stearothermophilus / metabolism*
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Heat-Shock Response / genetics*
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Helix-Turn-Helix Motifs
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Phosphorylation
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Promoter Regions, Genetic
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Protein Kinases / chemistry
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Protein Kinases / genetics
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Protein Kinases / metabolism*
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Protein Structure, Tertiary
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Repressor Proteins / antagonists & inhibitors*
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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Tandem Mass Spectrometry
Substances
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Bacterial Proteins
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CtsR protein, bacteria
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DNA, Bacterial
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Repressor Proteins
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Arginine
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Protein Kinases