内体分选转运复合体(endosomalsortingcomplex required for transport,ESCRT)是细胞中一个复杂的系统,该系统在病毒感染中起着“双刃剑”的作用,即它们能够被不同家族病毒劫持用于自身增殖,也能被宿主细胞利用对抗病毒的侵染。在病毒...内体分选转运复合体(endosomalsortingcomplex required for transport,ESCRT)是细胞中一个复杂的系统,该系统在病毒感染中起着“双刃剑”的作用,即它们能够被不同家族病毒劫持用于自身增殖,也能被宿主细胞利用对抗病毒的侵染。在病毒生命周期的不同阶段,病毒可以通过多种方式利用或限制ESCRT系统介导的生理过程,或者直接调控ESCRT系统的各蛋白组分的表达增加感染宿主的能力。ESCRT是由20多种蛋白质组成的复合体。根据其成分及其功能差异可以分为若干个复合物,即ESCRT-0、ESCRT-Ⅰ、ESCRT-Ⅱ、ESCRT-Ⅲ.展开更多
In nature, bacteria must sense copper and tightly regulate gene expression to evade copper toxicity. Here,we identify a new copper-responsive two-component system named DsbRS in the important human pathogen Pseudomona...In nature, bacteria must sense copper and tightly regulate gene expression to evade copper toxicity. Here,we identify a new copper-responsive two-component system named DsbRS in the important human pathogen Pseudomonas aeruginosa;in this system, DsbS is a sensor histidine kinase, and DsbR, its cognate response regulator, directly induces the transcription of genes involved in protein disulfide bond formation(Dsb)(i.e., the dsbDEG operon and dsbB). In the absence of copper, DsbS acts as a phosphatase toward DsbR, thus blocking the transcription of Dsb genes. In the presence of copper, the metal ion directly binds to the sensor domain of DsbS, and the Cys82 residue plays a critical role in this process. The copperbinding behavior appears to inhibit the phosphatase activity of DsbS, leading to the activation of DsbR.The copper resistance of the dsbRS knock-out mutant is restored by the ectopic expression of the dsbDEG operon, which is a DsbRS major target. Strikingly, cognates of the dsbRS-dsbDEG pair are widely distributed across eubacteria. In addition, a DsbR-binding site, which contains the consensus sequence 5’-TTA-N8-TTAA-3’, is detected in the promoter region of dsbDEG homologs in these species. These findings suggest that the regulation of Dsb genes by DsbRS represents a novel mechanism by which bacterial cells cope with copper stress.展开更多
文摘内体分选转运复合体(endosomalsortingcomplex required for transport,ESCRT)是细胞中一个复杂的系统,该系统在病毒感染中起着“双刃剑”的作用,即它们能够被不同家族病毒劫持用于自身增殖,也能被宿主细胞利用对抗病毒的侵染。在病毒生命周期的不同阶段,病毒可以通过多种方式利用或限制ESCRT系统介导的生理过程,或者直接调控ESCRT系统的各蛋白组分的表达增加感染宿主的能力。ESCRT是由20多种蛋白质组成的复合体。根据其成分及其功能差异可以分为若干个复合物,即ESCRT-0、ESCRT-Ⅰ、ESCRT-Ⅱ、ESCRT-Ⅲ.
基金supported by the National Key R&D Program of China(2016YFA0501503)the National Mega-project for Innovative Drugs of China(2019ZX09721001-004-003)+2 种基金the National Natural Science Foundation of China(31670136 31870127 and 81861138047)the Science and Technology Commission of Shanghai Municipality(19JC1416400)the State Key Laboratory of Drug Research(SIMM2003ZZ-03).
文摘In nature, bacteria must sense copper and tightly regulate gene expression to evade copper toxicity. Here,we identify a new copper-responsive two-component system named DsbRS in the important human pathogen Pseudomonas aeruginosa;in this system, DsbS is a sensor histidine kinase, and DsbR, its cognate response regulator, directly induces the transcription of genes involved in protein disulfide bond formation(Dsb)(i.e., the dsbDEG operon and dsbB). In the absence of copper, DsbS acts as a phosphatase toward DsbR, thus blocking the transcription of Dsb genes. In the presence of copper, the metal ion directly binds to the sensor domain of DsbS, and the Cys82 residue plays a critical role in this process. The copperbinding behavior appears to inhibit the phosphatase activity of DsbS, leading to the activation of DsbR.The copper resistance of the dsbRS knock-out mutant is restored by the ectopic expression of the dsbDEG operon, which is a DsbRS major target. Strikingly, cognates of the dsbRS-dsbDEG pair are widely distributed across eubacteria. In addition, a DsbR-binding site, which contains the consensus sequence 5’-TTA-N8-TTAA-3’, is detected in the promoter region of dsbDEG homologs in these species. These findings suggest that the regulation of Dsb genes by DsbRS represents a novel mechanism by which bacterial cells cope with copper stress.
