McsB Is a Protein Arginine Kinase That Phosphorylates and Inhibits the Heat-Shock Regulator CtsR
McsB Is a Protein Arginine Kinase That Phosphorylates and Inhibits the Heat-Shock Regulator CtsR
复制标题
DOI：
10.1126/science.1170088
复制
发表时间：
2009-06-05
期刊：
影响因子：
56.9
通讯作者：
Clausen, Tim
中科院分区：
文献类型：
--
作者：
Fuhrmann, Jakob;Schmidt, Andreas;Clausen, Tim
所有生物都面临各种环境压力，这些压力会导致蛋白质的错误折叠和聚集。为了消除受损的蛋白质，细胞开发了高效的应激反应和蛋白质质量控制系统。我们对细菌CtsR/MCSB应激反应进行了生化和结构分析。在与DNA的复合体中，CtsR阻遏物的晶体结构准确地定位了与热休克基因启动子区域高亲和力结合的关键残基。此外，MCSB的生化特性表明，MCSB特异性地磷酸化CtsR DNA结合域中的精氨酸残基，从而削弱其作为应激反应基因抑制因子的功能。CtsR/MCSB精氨酸磷酸开关的发现扩大了原核和真核转录调控中可能涉及的蛋白质修饰的范围。
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.