Identification of a family of four UDP-polypeptide N-acetylgalactosaminyl transferases in Cryptosporidium species

Mol Biochem Parasitol. 2013 Sep;191(1):24-7. doi: 10.1016/j.molbiopara.2013.08.002. Epub 2013 Aug 13.

Abstract

Although mucin-type O-glycans are critical for Cryptosporidium infection, the enzymes catalyzing their synthesis have not been studied. Here, we report four UDP N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyl transferases (ppGalNAc-Ts) from the genomes of C. parvum, C. hominis and C. muris. All are Type II membrane proteins which include a cytoplasmic tail, a transmembrane domain, a stem region, a glycosyltransferase family 2 domain and a C-terminal ricin B lectin domain. All are expressed during C. parvum infection in vitro, with Cp-ppGalNAc-T1 and -T4 expressed at 24 h and Cp-ppGalNAc-T2 and -T3 at 48 and 72 h post-infection, suggesting that their expression may be developmentally regulated. C. parvum sporozoite lysates display ppGalNAc-T enzymatic activity against non-glycosylated and pre-glycosylated peptides suggesting that they contain enzymes capable of glycosylating both types of substrates. The importance of mucin-type O-glycans in Cryptosporidium-host cell interactions raises the possibility that Cp-ppGalNAc-Ts may serve as targets for intervention in cryptosporidiosis.

Keywords: Cryptosporidium; Mucin; Mucin-like glycoprotein; O-glycosylation; UDP GalNAc:polypeptide N-acetylgalactosaminyl transferase.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cryptosporidium / enzymology*
  • Cryptosporidium / genetics*
  • DNA, Protozoan / chemistry
  • DNA, Protozoan / genetics
  • Gene Expression Profiling
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • N-Acetylgalactosaminyltransferases / genetics*
  • N-Acetylgalactosaminyltransferases / metabolism*
  • Protein Structure, Tertiary
  • Sequence Analysis, DNA

Substances

  • DNA, Protozoan
  • Membrane Proteins
  • N-Acetylgalactosaminyltransferases
  • polypeptide N-acetylgalactosaminyltransferase

Associated data

  • GENBANK/AY424895