Molecular mechanism of the one-component regulator RccR on bacterial metabolism and virulence

Author:

Zhu Yibo1,Mou Xingyu1,Song Yingjie2,Zhang Qianqian3,Sun Bo4,Liu Huanxiang3ORCID,Tang Hong1,Bao Rui1ORCID

Affiliation:

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

2. College of Life Science, Sichuan Normal University , Chengdu , China

3. Centre for Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences, Macao Polytechnic University , Macao 999078, China

4. Shanghai Advanced Research Institute, Chinese Academy of Sciences , Shanghai , China

Abstract

Abstract The regulation of carbon metabolism and virulence is critical for the rapid adaptation of pathogenic bacteria to host conditions. In Pseudomonas aeruginosa, RccR is a transcriptional regulator of genes involved in primary carbon metabolism and is associated with bacterial resistance and virulence, although the exact mechanism is unclear. Our study demonstrates that PaRccR is a direct repressor of the transcriptional regulator genes mvaU and algU. Biochemical and structural analyses reveal that PaRccR can switch its DNA recognition mode through conformational changes triggered by KDPG binding or release. Mutagenesis and functional analysis underscore the significance of allosteric communication between the SIS domain and the DBD domain. Our findings suggest that, despite its overall structural similarity to other bacterial RpiR-type regulators, RccR displays a more complex regulatory element binding mode induced by ligands and a unique regulatory mechanism.

Funder

Ministry of Science and Technology of China

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

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