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Title: Structure of a CutA1 divalent-cation tolerance protein from Cryptosporidium parvum, the protozoal parasite responsible for cryptosporidiosis

Cryptosporidiosis is an infectious disease caused by protozoan parasites from the Cryptosporidium species. Infection is associated with mild to severe diarrhea that usually resolves spontaneously in healthy human adults, but may lead to severe complications in young children and in 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, is reported 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-CutA1 up to 353 K. This robustness is corroborated by ¹H-¹⁵N HSQC spectra at 333 K that is characteristic of a folded protein, suggesting 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 β-bulgein β2 that protrudes P48 and S49 outside the β-sheet.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [7] ;  [6] ;  [8]
  1. Seattle Structural Genomics Center for Infectious Diesease, Seattle, WA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States)
  3. Seattle Structural Genomics Center for Infectious Diesease, Seattle, WA (United States); Beryllium, Bainbridge Island, WA (United States)
  4. Seattle Structural Genomics Center for Infectious Diesease, Seattle, WA (United States);Beryllium, Bainbridge Island, WA (United States)
  5. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  6. Seattle Structural Genomics Center for Infectious Diesease, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)
  7. Seattle Structural Genomics Center for Infectious Diesease, Seattle, WA (United States); Seattle Biomedical Research Institute, Seattle, WA (United States)
  8. Seattle Structural Genomics Center for Infectious Diesease, Seattle, WA (United States); Seattle Biomedical Research Institute, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)
Publication Date:
OSTI Identifier:
1193227
Report Number(s):
BNL--108113-2015-JA
Journal ID: ISSN 2053-230X; ACSFEN; R&D Project: LS001
Grant/Contract Number:
SC00112704
Type:
Accepted Manuscript
Journal Name:
Acta Crystallographica. Section F, Structural biology Communications
Additional Journal Information:
Journal Volume: 71; Journal Issue: 5; Journal ID: ISSN 2053-230X
Publisher:
International Union of Crystallography
Research Org:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org:
USDOE Office of Science (SC)
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE Cryptosporidium parvum; divalent-cation tolerance protein; CutA1; cryptosporidiosis