Functional and structural characterization of Akkermansia muciniphila thioredoxin domain-containing protein Amuc_2173

Akkermansia muciniphila is a beneficial bacterium that colonizes the human intestinal mucosa. Its colonization and function require the assistance of antioxidant proteins to cope with oxidative stress. In this work, we demonstrated that the A. muciniphila thioredoxin domain-containing protein Amuc_2173 possesses thiol-disulfide oxidoreductase activity and that this activity does not require the involvement of its coiled-coil CTD. Further, we determined the structure of the thioredoxin domain of Amuc_2173, which adopts the thioredoxin fold of the ResA/DsbE subfamily. In addition, our activity assays of cysteine mutations demonstrated that the cysteine residues in the CXXC motif are crucial for the thiol-disulfide oxidoreductase activity of Amuc_2173. Our results provide experimental evidence for the antioxidant potential of Amuc_2173.