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

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

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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.

Pseudomonas aeruginosatranscription regulatorTetRprotein-structurevirulence

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

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Center of Infectious Diseases,Division of Infectious Diseases in State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu 610041,China

Accurate Biotechnology(Hunan)Co.,Ltd,Changsha 410006,China

College of Life Science,Sichuan Normal University,Chengdu 610101,China

Key Laboratory of Biodiversity and Environment on the Qinghai-Tibetan Plateau,Ministry of Education,School of Ecology and Environment,Tibet University,Lhasa 850000,China

Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai 201210,China

Department of Geriatrics and National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu 610041,China

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Ministry of Science and Technology of ChinaMinistry of Science and Technology of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaTianjin Synthetic Biotechnology Innovation Capacity Improvement ActionTibet Science Foundation grant

2022YFC23037002021YFA1301900818716153222204032070049TSBICIP-KJGG-008XZ202001ZY0036 N

2024

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子:0.806
ISSN:1674-7305
年,卷(期):2024.67(5)