Efficient inhibition of cathepsin B by a secreted type 1 cystatin of Fasciola gigantica

Siricoon, Sinee; Grams, Suksiri Vichasri; Grams, Rudi

doi:10.1016/j.molbiopara.2012.10.003

Cited by 26 publications

(44 citation statements)

References 41 publications

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“…In addition, the presence of multidomain proteins are not the only novelty in the cystatin family, several I25A cystatins from unicellular eukaryotic organisms have gained the signal peptide, which is absent in the majority of metazoan and eukaryotic I25A cystatins. The presence of signal peptide as observed in some unicellular eukaryotic I25A cystatins (Kordis and Turk, 2009) and in Fasciola gigantica (Siricoon et al, 2012) may lead to the gain of novel defense functions.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, an unusual secreted form of I25A member was characterized in F. gigantica (Siricoon et al, 2012). Although this awkward cystatin does present a signal peptide, typical of I25B proteins, sequence analysis does correlate it to the I25A subfamily.…”

Section: Discussionmentioning

confidence: 99%

“…Although this awkward cystatin does present a signal peptide, typical of I25B proteins, sequence analysis does correlate it to the I25A subfamily. Nevertheless, Siricoon et al (2012) provided evidence of a secreted form of a cystatin protein in Platyhelminthes that was again observed in the intestinal epithelium in all developmental stages. Moreover, the secreted 125A protein was also found expressed in the prostate gland in the adult stage of F. gigantica , which suggests a regulative role of cysteine protease activity in reproductive system.…”

Section: Discussionmentioning

confidence: 99%

“…According to MEROPS classification, proteins containing a single inhibitor unit are termed simple inhibitor, and those containing multiple inhibitor units are termed as a compound inhibitor (Rawlings et al, 2014). However, several proteins containing cystatin domains cannot be easily included in a classification scheme, resulting in a number of cystatin family members that remain without classification in the subfamily level (Cornwall et al, 2003; Kordis and Turk, 2009; Siricoon et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

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Evolutionary analysis of the cystatin family in three Schistosoma species

et al. 2014

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The cystatin family comprises cysteine protease inhibitors distributed in 3 subfamilies (I25A–C). Family members lacking cystatin activity are currently unclassified. Little is known about the evolution of Schistosoma cystatins, their physiological roles, and expression patterns in the parasite life cycle. The present study aimed to identify cystatin homologs in the predicted proteome of three Schistosoma species and other Platyhelminthes. We analyzed the amino acid sequence diversity focused in the identification of protein signatures and to establish evolutionary relationships among Schistosoma and experimentally validated human cystatins. Gene expression patterns were obtained from different developmental stages in Schistosoma mansoni using microarray data. In Schistosoma, only I25A and I25B proteins were identified, reflecting little functional diversification. I25C and unclassified subfamily members were not identified in platyhelminth species here analyzed. The resulting phylogeny placed cystatins in different clades, reflecting their molecular diversity. Our findings suggest that Schistosoma cystatins are very divergent from their human homologs, especially regarding the I25B subfamily. Schistosoma cystatins also differ significantly from other platyhelminth homologs. Finally, transcriptome data publicly available indicated that I25A and I25B genes are constitutively expressed thus could be essential for schistosome life cycle progression. In summary, this study provides insights into the evolution, classification, and functional diversification of cystatins in Schistosoma and other Platyhelminthes, improving our understanding of parasite biology and opening new frontiers in the identification of novel therapeutic targets against helminthiases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evolutionary analysis of the cystatin family in three Schistosoma species

et al. 2014

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“…Cystatin C is a 13-kDa secreted protein that is broadly expressed and is present in all human biological fluids and tissues examined with very high concentrations in seminal plasma and cerebrospinal fluid (2). As a potent inhibitor of C1 family of cysteine proteases including the lysosomal cysteine proteases cathepsins B, H, L, and S, cystatin C is thought to play a protective role against tissue destruction, whereas other roles in bone resorption, tumor metastasis, protein processing, and parasite infections have also been proposed (3)(4)(5)(6)(7). Cst3 resides on human chromosome 20 and mouse chromosome 2, where it clusters with several other cystatin family 2 members including members of a reproductive subgroup comprising Cst8 (cystatin-related epididymal spermatogenic (CRES) 2 ), Cst9 (testatin), Cst11 (CRES2), Cst12 (CRES3), cystatin E2, and others (8 -11).…”

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confidence: 99%

Fertility Defects in Mice Expressing the L68Q Variant of Human Cystatin C

Whelly¹,

Serobian²,

Borchardt³

et al. 2014

Journal of Biological Chemistry

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Background: The L68Q variant of cystatin C is highly amyloidogenic forming aggregates in individuals with HCCAA. Results: Spermatozoa from mice expressing human L68Q cystatin C exhibit fertility defects and increased levels of amyloid. Conclusion: L68Q epididymal fluid containing cystatin C amyloid is harmful for sperm function. Significance: Amyloid in the reproductive tract may contribute to male factor infertility.

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Giardia intestinalis cystatin is a potent inhibitor of papain, parasite cysteine proteases and, to a lesser extent, human cathepsin B

2019

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Cystatins are important regulators of papain‐like cysteine proteases. In the protozoan parasite Giardia intestinalis, papain‐like cysteine proteases play an essential role in the parasite's biology and pathogenicity. Here, we characterized a cysteine protease inhibitor of G. intestinalis that belongs to type‐I‐cystatins. The parasite cystatin is shown to be a strong inhibitor of papain (Ki ≈ 0.3 nm) and three parasite cysteine proteases (CP14019, CP16160 and CP16779, Ki ≈ 0.9–5.8 nm), but a weaker inhibitor of human cathepsin B (Ki ≈ 79.9 nm). The protein localizes mainly in the cytoplasm. Together, these data suggest that cystatin of G. intestinalis plays a role in the regulation of cysteine protease activities in the parasite and, possibly, in the interaction with the host.

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Efficient inhibition of cathepsin B by a secreted type 1 cystatin of Fasciola gigantica

Cited by 26 publications

References 41 publications

Evolutionary analysis of the cystatin family in three Schistosoma species

Evolutionary analysis of the cystatin family in three Schistosoma species

Fertility Defects in Mice Expressing the L68Q Variant of Human Cystatin C

Giardia intestinalis cystatin is a potent inhibitor of papain, parasite cysteine proteases and, to a lesser extent, human cathepsin B

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