title: A Giardia duodenalis gene encoding a protein with multiple repeats of a toxin homologue.
abstract: A gene, CRP136, from the intestinal protozoan parasite Giardia duodenalis, expressed at a high level in a metronidazole-resistant line, encodes a 136 kDa protein with 23 copies of a 40 amino acid repeat. The protein is cysteine-rich and has the typical membrane-spanning region and CXXC amino acid motifs of a family of Giardia cysteine-rich surface proteins (CRSPs). The repeat unit in CRP136, shares 57% homology with the gene encoding the precursor of the sarafotoxins, a group of snake toxins from the burrowing adder known to cause symptoms similar to those of humans acutely infected with Giardia. The sarafotoxins are low molecular weight sulphydryl cross-linked peptides which are proteolytically cleaved from a precursor polyprotein. CRP136 has homology over the entire length of the sarafotoxin precursor, and the repeats are of the same length. Thus CRP136 represents the first evidence for a potential Giardia toxin. The genomic copy number of CRP136 appears to be the same in both the parent and drug-resistant lines and expression of this gene, and at least one other, is associated with a conserved partial duplication, but not amplification, of one chromosome.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Chen
authors.forename: J A
authors.initials: JA
authors.lastname: Upcroft
authors.forename: P
authors.initials: P
authors.lastname: Upcroft
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002875:Chromosomes; D004351:Drug Resistance; D017125:Genes, Protozoan; D015698:Genomic Library; D005872:Giardia / Q000235:genetics*; D008795:Metronidazole / Q000494:pharmacology; D008969:Molecular Sequence Data; D005810:Multigene Family; D015800:Protozoan Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020449:Repetitive Sequences, Amino Acid; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014757:Viper Venoms / Q000235:genetics
chemical_list: D000981:Antiprotozoal Agents; C097377:CRP136 protein, Giardia duodenalis; D015800:Protozoan Proteins; D012333:RNA, Messenger; D014757:Viper Venoms; D008795:Metronidazole