Regulation of DNA-binding activity of the Staphylococcus aureus catabolite control protein A by copper (II)-mediated oxidation

Xiangwen Liao; Huinan Li; Yu Guo; Fang Yang; Yushou Chen; Xiaojun He; Hongyan Li; Wei Xia; Zong-Wan Mao; Hongzhe Sun

doi:10.1016/j.jbc.2022.101587

Regulation of DNA-binding activity of the Staphylococcus aureus catabolite control protein A by copper (II)-mediated oxidation

J Biol Chem. 2022 Mar;298(3):101587. doi: 10.1016/j.jbc.2022.101587. Epub 2022 Jan 13.

Authors

Xiangwen Liao¹, Huinan Li², Yu Guo³, Fang Yang², Yushou Chen⁴, Xiaojun He², Hongyan Li⁵, Wei Xia⁶, Zong-Wan Mao⁷, Hongzhe Sun⁸

Affiliations

¹ MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, China; School of Pharmacy, Jiangxi Science &Technology Normal University, Nanchang, China.
² MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, China.
³ MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, China; CAS Key Laboratory of Tropical Marine Bio Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China; Southern Marine Science and Engineering Guangdong Laboratory, Guangzhou, China.
⁴ School of Pharmacy, Jiangxi Science &Technology Normal University, Nanchang, China.
⁵ Department of Chemistry, The University of Hong Kong, Hong Kong SAR, China.
⁶ MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, China. Electronic address: xiawei5@mail.sysu.edu.cn.
⁷ MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, China. Electronic address: cesmzw@mail.sysu.edu.cn.
⁸ Department of Chemistry, The University of Hong Kong, Hong Kong SAR, China. Electronic address: hsun@hku.hk.

Abstract

Catabolite control protein A (CcpA) of the human pathogen Staphylococcus aureus is an essential DNA regulator for carbon catabolite repression and virulence, which facilitates bacterial survival and adaptation to a changing environment. Here, we report that copper (II) signaling mediates the DNA-binding capability of CcpA in vitro and in vivo. Copper (II) catalyzes the oxidation of two cysteine residues (Cys216 and Cys242) in CcpA to form intermolecular disulfide bonds between two CcpA dimers, which results in the formation and dissociation of a CcpA tetramer of CcpA from its cognate DNA promoter. We further demonstrate that the two cysteine residues on CcpA are important for S. aureus to resist host innate immunity, indicating that S. aureus CcpA senses the redox-active copper (II) ions as a natural signal to cope with environmental stress. Together, these findings reveal a novel regulatory mechanism for CcpA activity through copper (II)-mediated oxidation.

Keywords: Staphylococcus aureus; catabolite control protein A; copper; oxidation; regulatory mechanism.

MeSH terms

Bacterial Proteins* / chemistry
Bacterial Proteins* / metabolism
Cations, Divalent
Copper* / chemistry
Copper* / metabolism
Cysteine / chemistry
Cysteine / metabolism
DNA, Bacterial* / metabolism
Oxidation-Reduction
Repressor Proteins* / chemistry
Repressor Proteins* / metabolism
Staphylococcus aureus* / metabolism

Substances

Bacterial Proteins
Cations, Divalent
DNA, Bacterial
Repressor Proteins
catabolite control proteins, bacteria
Copper
Cysteine