Ac-FAR-1, a 20 kDa fatty acid- and retinol-binding protein secreted by adult Ancylostoma caninum hookworms: gene transcription pattern, ligand binding properties and structural characterisation

Mol Biochem Parasitol. 2003 Jan;126(1):63-71. doi: 10.1016/s0166-6851(02)00253-0.

Abstract

Antibody against adult Ancylostoma caninum excretory-secretory (ES) products was used to immunoscreen a cDNA expression library leading to the isolation of cDNAs encoding putative hookworm fatty-acid and retinol-binding proteins. Ac-far-1 and Ac-far-2 cDNAs encode open reading frames corresponding to approximately 20kDa proteins with 91 percent amino acid identity. Ac-FAR-1 and Ac-FAR-2 exhibit clear similarities to other FARs of parasitic nematodes, most closely to two of the FAR proteins of Caenorhabditis elegans (Ce-FAR-1 and Ce-FAR-2). By reverse transcriptase polymerase chain reaction (RT-PCR) assay, Ac-far-1 mRNA was detected in both adult and third-stage larvae of A. caninum. However, the respective proteins were detectable by immunoblot only in adult hookworm ES products and adult extracts. Using fluorescence-based binding assays, bacterial recombinant Ac-FAR-1 was found to bind fatty acids and retinol (Vitamin A) with dissociation constants in the micromolar region. Circular dichroism spectra indicated that Ac-FAR-1 possesses a high level of alpha-helix, similar to Ov-FAR-1 from Onchocerca volvulus. This is the first demonstration of a functional FAR secreted by adult hookworms and provides further evidence that FAR proteins secreted by parasitic nematodes are crucial to parasitism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Ancylostoma / genetics
  • Ancylostoma / metabolism*
  • Ancylostomiasis / parasitology
  • Animals
  • Base Sequence
  • Carrier Proteins* / chemistry
  • Carrier Proteins* / genetics
  • Carrier Proteins* / metabolism
  • Cloning, Molecular
  • Dogs
  • Fatty Acids / metabolism*
  • Helminth Proteins* / chemistry
  • Helminth Proteins* / genetics
  • Helminth Proteins* / metabolism
  • Ligands
  • Molecular Sequence Data
  • Phylogeny
  • Recombinant Proteins / analysis
  • Retinol-Binding Proteins* / chemistry
  • Retinol-Binding Proteins* / genetics
  • Retinol-Binding Proteins* / metabolism
  • Sequence Alignment
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • Fatty Acids
  • Helminth Proteins
  • Ligands
  • Recombinant Proteins
  • Retinol-Binding Proteins

Associated data

  • GENBANK/AF529181
  • GENBANK/AF533365