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Functional characterization of single-domain cystatin-like cysteine proteinase inhibitors expressed by the trematodeFasciola hepatica
- Source :
- Parasitology. 144:1695-1707
- Publication Year :
- 2017
- Publisher :
- Cambridge University Press (CUP), 2017.
-
Abstract
- SUMMARYCystatins are small, phylogenetically conserved proteins that are tight-binding inhibitors of cysteine proteinases. The liver flukeFasciola hepaticauses a diverse set of cysteine proteinases of the papain superfamily for host invasion, immune evasion and nutrition, but little is known about the regulation of these enzymes. The aim of this work is to characterize the cystatin repertoire ofF. hepatica. For this purpose, we first surveyed the available sequence databases, identifying three differentF. hepaticasingle-domain cystatins. In agreement with thein silicopredictions, at least three small proteins with cysteine proteinase binding activity were identified. Phylogenetic analyses showed that the three cystatins (named FhStf-1, -2 and -3) are members of the I25A subfamily (stefins). Whereas FhStf-1 grouped with classical stefins, FhStf-2 and 3 fell in a divergent stefin subgroup unusually featuring signal peptides. Recombinant rFhStf-1, -2 and -3 had potent inhibitory activity againstF. hepaticacathepsinLcysteine proteinases but differed in their capacity to inhibit mammalian cathepsinB,LandC. FhStf-1 was localized in theF. hepaticareproductive organs (testes and ovary), and at the surface lamella of the adult gut, where it may regulate cysteine proteinases related with reproduction and digestion, respectively. FhStf-1 was also detected amongF. hepaticaexcretion–secretion (E/S) products of adult flukes. This suggests that it is secreted by non-classical secretory pathway and that it may interact with host lysosomal cysteine proteinases.
- Subjects :
- 0301 basic medicine
Signal peptide
Cathepsin L
Cysteine Proteinase Inhibitors
Cathepsin C
Cathepsin B
03 medical and health sciences
Hepatica
parasitic diseases
Escherichia coli
Animals
Humans
Fasciola hepatica
Amino Acid Sequence
Phylogeny
Organisms, Genetically Modified
biology
Helminth Proteins
biology.organism_classification
Cystatins
Recombinant Proteins
030104 developmental biology
Infectious Diseases
Biochemistry
biology.protein
Cattle
Animal Science and Zoology
Parasitology
Cystatin
Sequence Alignment
Cysteine
Subjects
Details
- ISSN :
- 14698161 and 00311820
- Volume :
- 144
- Database :
- OpenAIRE
- Journal :
- Parasitology
- Accession number :
- edsair.doi.dedup.....1d833c6fddfe1d769aa91517d9e80265