Pseudomonas aeruginosa regulator PvrA binds simultaneously to multiple pseudo-palindromic sites for efficient transcription activation  

作　　者：Yibo Zhu Bingnan Luo Xingyu Mou Yingjie Song Yonghong Zhou Yongbo Luo Bo Sun Youfu Luo Hong Tang Zhaoming Su Rui Bao 

机构地区：[1]Center of Infectious Diseases,Division of Infectious Diseases in State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu 610041,China [2]Department of Geriatrics and National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu 610041,China [3]Key Laboratory of Biodiversity and Environment on the Qinghai-Tibetan Plateau,Ministry of Education,School of Ecology and Environment,Tibet University,Lhasa 850000,China [4]Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai 201210,China [5]College of Life Science,Sichuan Normal University,Chengdu 610101,China [6]Accurate Biotechnology(Hunan)Co.,Ltd,Changsha 410006,China

出　　处：《Science China(Life Sciences)》2024年第5期900-912,共13页中国科学（生命科学英文版）

基　　金：supported by the Ministry of Science and Technology of China(2022YFC2303700,2021YFA1301900);The National Natural Science Foundation of China(81871615,32222040,32070049);Tianjin Synthetic Biotechnology Innovation Capacity Improvement Action(TSBICIP-KJGG-008);supported in part by a Tibet Science Foundation grant(XZ202001ZY0036 N)to Yonghong Zhou。

摘　　要：Tetracycline repressor(TetR)family regulators(TFRs)are the largest group of DNA-binding transcription factors and are widely distributed in bacteria and archaea.TFRs play vital roles in controlling the expression of various genes and regulating diverse physiological processes.Recently,a TFR protein Pseudomonas virulence regulator A(PvrA),was identified from Pseudomonas aeruginosa as the transcriptional activator of genes involved in fatty acid utilization and bacterial virulence.Here,we show that PvrA can simultaneously bind to multiple pseudo-palindromic sites and upregulate the expression levels of target genes.Cryo-electron microscopy(cryo-EM)analysis indicates the simultaneous DNA recognition mechanism of PvrA and suggests that the bound DNA fragments consist of a distorted B-DNA double helix.The crystal structure and functional analysis of PvrA reveal a hinge region that secures the correct domain motion for recognition of the promiscuous promoter.Additionally,our results showed that mutations disrupting the regulatory hinge region have differential effects on biofilm formation and pyocyanin biosynthesis,resulting in attenuated bacterial virulence.Collectively,these findings will improve the understanding of the relationship between the structure and function of the TetR family and provide new insights into the mechanism of regulation of P.aeruginosa virulence.

关 键 词：Pseudomonas aeruginosa transcription regulator TetR protein-structure VIRULENCE 

分 类 号：R378.991[医药卫生—病原生物学]