Some Properties of the C. elegans Multicopper Oxidase F21D5.3, an Ortholog of Human Ceruloplasmin.

This study identified an oxidase-positive protein in the plasma membrane fraction of the C. elegans N2 strain. The protein with a molecular weight of approximately 85 kDa reacted with antibodies against human and mouse, but not rat, ceruloplasmin and exhibited oxidase activity. Bioinformatic analysis revealed that the F21D5.3 protein possesses four copper-binding sites, similar to those in other multicopper oxidases (MCOs), and plastocyanin-like domains characteristic of MCOs. However, neither an iron-binding domain nor ferroxidase activity, typical features of MCOs, were detected through in silico analysis and or in-gel assays. Despite the absence of ferroxidase activity, these findings suggest that the protein may be the product of the F21D5.3 gene, an ortholog of MCOs in C. elegans. Heat map analysis indicated F21D5.3 expression in the entero-rectal valve cells and both the anterior and posterior intestines. Among the genes associated with copper transport, only cua-1 exhibited a similar expression pattern. In the C. elegans cua-1(H828Q) strain, which mimics a mutation in human ATP7B linked to Wilson's disease (WD), oxidase activity was also observed. Notably, both strains showed reduced oxidase activity when cultured with silver nanoparticles (AgNPs). These findings highlight the potential of the cua-1(H828Q) strain as a model for studying copper and iron metabolism and for developing therapeutic strategies for WD.