PNNL

Abstract

Cryptosporidiosis is an infectious disease caused by protozoan parasites from the Cryptosporidium species. Infection is associated with mild to severe diarrhea that is usually resolved spontaneously in healthy human adults but may lead to severe complications in young children and immunocompromised patients. The genome of Cryptosporidium parvum contains a gene, CUTA_CRYPI, that may play a role in regulating the intracellular concentration of copper, a toxic element if left unchecked. Here we report the crystal structure for this CutA1 protein, Cp-CutA1, at 2.0 Å resolution (4E98). As observed for other CutA1 structures, the 117-residue protein is a trimer with a core ferrodoxin-like fold. Circular dichroism spectroscopy shows little unfolding of Cp-CutA up to 353 K. This robostness is corroborated by 1H-15N HSQC spectra at 333 K that is characteristic of a folded protein, suggesting the NMR spectroscopy may be a useful tool to further probe the function of the CutA1 proteins. While robust, Cp-CutA1 is not as stable as the homologous protein from a hyperthermophile, perhaps due to a wide ß-bulge in ß2 that protrudes P48 and S49 outside the ß-sheet.