A periplasmic cupredoxin with a green CuT1.5 center is involved in bacterial copper tolerance.
Anne DurandMélanie FouesnardMarie-Line BourbonAnne-Soisig SteunouElisabeth LojouPierre DorletSoufian OuchanePublished in: Metallomics : integrated biometal science (2022)
The importance of copper resistance pathways in pathogenic bacteria is now well recognized, since macrophages use copper to fight bacterial infections. Additionally, considering the increase of antibiotic resistance, growing attention is given to the antimicrobial properties of copper. It is of primary importance to understand how bacteria deal with copper. The Cu-resistant cuproprotein CopI is present in many human bacterial pathogens and environmental bacteria and crucial under microaerobiosis (conditions for most pathogens to thrive within their host). Hence, understanding its mechanism of function is essential. CopI proteins share conserved histidine, cysteine, and methionine residues that could be ligands for different copper binding sites, among which the cupredoxin center could be involved in the protein function. Here, we demonstrated that Vibrio cholerae and Pseudomonas aeruginosa CopI restore the Cu-resistant phenotype in the Rubrivivax gelatinosus ΔcopI mutant. We identified that Cys125 (ligand in the cupredoxin center) and conserved histidines and methionines are essential for R. gelatinosus CopI (RgCopI) function. We also performed spectroscopic analyses of the purified RgCopI protein and showed that it is a green cupredoxin able to bind a maximum of three Cu(II) ions: (i) a green Cu site (CuT1.5), (ii) a type 2 Cu binding site (T2) located in the N-terminal region, and (iii) a third site with a yet unidentified location. CopI is therefore one member of the poorly described CuT1.5 center cupredoxin family. It is unique, since it is a single-domain cupredoxin with more than one Cu site involved in Cu resistance.
Keyphrases
- aqueous solution
- pseudomonas aeruginosa
- oxide nanoparticles
- metal organic framework
- staphylococcus aureus
- endothelial cells
- cystic fibrosis
- transcription factor
- working memory
- amino acid
- escherichia coli
- risk assessment
- gram negative
- small molecule
- climate change
- fluorescent probe
- acinetobacter baumannii
- human health
- induced pluripotent stem cells
- single molecule
- life cycle