A new multi-domain member of the cystatin superfamily expressed by Fasciola hepatica

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Journal Article
International Journal for Parasitology, 2005, 35 pp. 1115 - 1125
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Cystatins are systeine protease inhibitors that are widespread in the plant and animal kingdoms. Cystatins are expressed by helminth parasites that may emply these proteins to regulate parasite cysteine protease activity and to modulate host immune responses. Here, we describe the cloning of a cDNA encoding a high molecular weight protein of Fasciola hepatica thay contains two domains with significant identity to the cardinal cystatin signatures and four domains with degenerated sydtatin signatures. This is the first report of a multi-domain cystatin inan invertebrate species. While cystatins are divided into three evolutionary related families, our phylogenetic analysis shows that all cystatin domains within this protein, like several other helminth cystatins, belong to the cystatin family 2. The DNA region encoding the domian 4 that is the nest conserved at the level of tis cystatin signatures was expressed in Drosophila cells and a recombitnant protein was produced and purified. This protein was a potent inhibitor of the papain and of the major cysteine protease of F. hepatica, the cathepsin L1.
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