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Comparative analysis of cystatin superfamily in platyhelminths.

Guo A - PLoS ONE (2015)

Bottom Line: However, it is noteworthy that cestode cystatins had two tandem repeated domains, although the second tandem repeated domain did not contain a cystatin-like domain, which has not been previously reported.Although no conserved disulfide bond was found in T. solium cystatin, the models of T. solium cystatin and chicken cystatin corresponded at the site of the first disulfide bridge of the chicken cystatin.The same results were obtained for other cestode cystatins.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease, Yangzhou, Jiangsu, China.

ABSTRACT
The cystatin superfamily is comprised of cysteine proteinase inhibitors and encompasses at least 3 subfamilies: stefins, cystatins and kininogens. In this study, the platyhelminth cystatin superfamily was identified and grouped into stefin and cystatin subfamilies. The conserved domain of stefins (G, QxVxG) was observed in all members of platyhelminth stefins. The three characteristics of cystatins, the cystatin-like domain (G, QxVxG, PW), a signal peptide, and one or two conserved disulfide bonds, were observed in platyhelminths, with the exception of cestodes, which lacked the conserved disulfide bond. However, it is noteworthy that cestode cystatins had two tandem repeated domains, although the second tandem repeated domain did not contain a cystatin-like domain, which has not been previously reported. Tertiary structure analysis of Taenia solium cystatin, one of the cestode cystatins, demonstrated that the N-terminus of T. solium cystatin formed a five turn α-helix, a five stranded β-pleated sheet and a hydrophobic edge, similar to the structure of chicken cystatin. Although no conserved disulfide bond was found in T. solium cystatin, the models of T. solium cystatin and chicken cystatin corresponded at the site of the first disulfide bridge of the chicken cystatin. However, the two models were not similar regarding the location of the second disulfide bridge of chicken cystatin. These results showed that T. solium cystatin and chicken cystatin had similarities and differences, suggesting that the biochemistry of T. solium cystatin could be similar to chicken cystatin in its inhibitory function and that it may have further functional roles. The same results were obtained for other cestode cystatins. Phylogenetic analysis showed that cestode cystatins constituted an independent clade and implied that cestode cystatins should be considered to have formed a new clade during evolution.

No MeSH data available.


Comparison of tertiary structures for chicken and T. solium cystatins.The 3D structures for chicken cystain (A) and T. solium cystatin (B) are shown. The cystatin models of chicken and T. solium are superimposed in (C). The opposite side of the (C) map are enlarged and shown in (D).
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pone.0124683.g004: Comparison of tertiary structures for chicken and T. solium cystatins.The 3D structures for chicken cystain (A) and T. solium cystatin (B) are shown. The cystatin models of chicken and T. solium are superimposed in (C). The opposite side of the (C) map are enlarged and shown in (D).

Mentions: Cestode cystatins with two tandem repeated domains and without conserved disulfide bonds have not been reported previously. It is intriguing to explore whether they have similar structural features to chicken cystatin. The crystal structure of chicken cystatin consists mainly of a five string α-helix and a five-stranded β-pleated sheet [1]. N-terminal Gly residue, QXVXG residues sited at the first β-hairpin loop and Pro-Trp residues sited at the second β-hairpin loop forming a hydrophobic edge to penetrate into the active site cleft of papins have been discussed in detail [43, 44, 49, 50]. The 3D structure of chicken cystatin [32] and T. solium cystatin are shown in Fig 4A and 4B, respectively. Although the structure of the extra C-terminal repeat domain of T. solium cystatin was difficult to predict, a superimposed diagram of 3D models for T. solium cystatin and chicken cystatin indicates that their papain inhibitory loop (G, QXVXG, PW) almost overlaps (Fig 4C). Although no conserved disulfide bond was found in T.solium cystatin, the models of T.solium cystatin and chicken cystatin corresponded at the site of the first disulfide bridge of the chicken cystatin, which may be explained by other kinds of bonds, such as a hydrogen bond. The two models were different regarding the location of the second disulfide bridge of chicken cystatin (Fig 4D). The same results were also obtained for other cestode cystatins (S3 Fig). These results showed that the models of cestode cystatins and chicken cystatin had both similarities and differences, suggesting that the biochemistry of cestode cystatins could be similar to chicken cystatin in its inhibitory function and they may have additional functional roles. This result is in disagreement with a recent study that has suggested it was not possible to identify cystatin homologs in E. granulosus, H. microstoma and T. solium [19]. In addition, excepting cestode cystatins, all predicted models of platyhelminth stefins and cystatins exhibited the similar conserved α-helix and β-pleat and the functional hydrophobic edge features that find in the human stefin [33, 51] and chicken cystatin models [32], respectively (not shown). Previous studies have shown that the structure of the plant inhibitor oryzacystatin possesses the same cystatin fold as animal cystatin, which has the ability to inhibit cysteine proteinase [52]. These results suggest that the biochemistry of the platyhelminth cystatin superfamily could be similar to chicken cystatin and human stefin in its inhibitory function, and it is possible that cestode cystatins may have further, as yet undefined, functional roles.


Comparative analysis of cystatin superfamily in platyhelminths.

Guo A - PLoS ONE (2015)

Comparison of tertiary structures for chicken and T. solium cystatins.The 3D structures for chicken cystain (A) and T. solium cystatin (B) are shown. The cystatin models of chicken and T. solium are superimposed in (C). The opposite side of the (C) map are enlarged and shown in (D).
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Related In: Results  -  Collection

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pone.0124683.g004: Comparison of tertiary structures for chicken and T. solium cystatins.The 3D structures for chicken cystain (A) and T. solium cystatin (B) are shown. The cystatin models of chicken and T. solium are superimposed in (C). The opposite side of the (C) map are enlarged and shown in (D).
Mentions: Cestode cystatins with two tandem repeated domains and without conserved disulfide bonds have not been reported previously. It is intriguing to explore whether they have similar structural features to chicken cystatin. The crystal structure of chicken cystatin consists mainly of a five string α-helix and a five-stranded β-pleated sheet [1]. N-terminal Gly residue, QXVXG residues sited at the first β-hairpin loop and Pro-Trp residues sited at the second β-hairpin loop forming a hydrophobic edge to penetrate into the active site cleft of papins have been discussed in detail [43, 44, 49, 50]. The 3D structure of chicken cystatin [32] and T. solium cystatin are shown in Fig 4A and 4B, respectively. Although the structure of the extra C-terminal repeat domain of T. solium cystatin was difficult to predict, a superimposed diagram of 3D models for T. solium cystatin and chicken cystatin indicates that their papain inhibitory loop (G, QXVXG, PW) almost overlaps (Fig 4C). Although no conserved disulfide bond was found in T.solium cystatin, the models of T.solium cystatin and chicken cystatin corresponded at the site of the first disulfide bridge of the chicken cystatin, which may be explained by other kinds of bonds, such as a hydrogen bond. The two models were different regarding the location of the second disulfide bridge of chicken cystatin (Fig 4D). The same results were also obtained for other cestode cystatins (S3 Fig). These results showed that the models of cestode cystatins and chicken cystatin had both similarities and differences, suggesting that the biochemistry of cestode cystatins could be similar to chicken cystatin in its inhibitory function and they may have additional functional roles. This result is in disagreement with a recent study that has suggested it was not possible to identify cystatin homologs in E. granulosus, H. microstoma and T. solium [19]. In addition, excepting cestode cystatins, all predicted models of platyhelminth stefins and cystatins exhibited the similar conserved α-helix and β-pleat and the functional hydrophobic edge features that find in the human stefin [33, 51] and chicken cystatin models [32], respectively (not shown). Previous studies have shown that the structure of the plant inhibitor oryzacystatin possesses the same cystatin fold as animal cystatin, which has the ability to inhibit cysteine proteinase [52]. These results suggest that the biochemistry of the platyhelminth cystatin superfamily could be similar to chicken cystatin and human stefin in its inhibitory function, and it is possible that cestode cystatins may have further, as yet undefined, functional roles.

Bottom Line: However, it is noteworthy that cestode cystatins had two tandem repeated domains, although the second tandem repeated domain did not contain a cystatin-like domain, which has not been previously reported.Although no conserved disulfide bond was found in T. solium cystatin, the models of T. solium cystatin and chicken cystatin corresponded at the site of the first disulfide bridge of the chicken cystatin.The same results were obtained for other cestode cystatins.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease, Yangzhou, Jiangsu, China.

ABSTRACT
The cystatin superfamily is comprised of cysteine proteinase inhibitors and encompasses at least 3 subfamilies: stefins, cystatins and kininogens. In this study, the platyhelminth cystatin superfamily was identified and grouped into stefin and cystatin subfamilies. The conserved domain of stefins (G, QxVxG) was observed in all members of platyhelminth stefins. The three characteristics of cystatins, the cystatin-like domain (G, QxVxG, PW), a signal peptide, and one or two conserved disulfide bonds, were observed in platyhelminths, with the exception of cestodes, which lacked the conserved disulfide bond. However, it is noteworthy that cestode cystatins had two tandem repeated domains, although the second tandem repeated domain did not contain a cystatin-like domain, which has not been previously reported. Tertiary structure analysis of Taenia solium cystatin, one of the cestode cystatins, demonstrated that the N-terminus of T. solium cystatin formed a five turn α-helix, a five stranded β-pleated sheet and a hydrophobic edge, similar to the structure of chicken cystatin. Although no conserved disulfide bond was found in T. solium cystatin, the models of T. solium cystatin and chicken cystatin corresponded at the site of the first disulfide bridge of the chicken cystatin. However, the two models were not similar regarding the location of the second disulfide bridge of chicken cystatin. These results showed that T. solium cystatin and chicken cystatin had similarities and differences, suggesting that the biochemistry of T. solium cystatin could be similar to chicken cystatin in its inhibitory function and that it may have further functional roles. The same results were obtained for other cestode cystatins. Phylogenetic analysis showed that cestode cystatins constituted an independent clade and implied that cestode cystatins should be considered to have formed a new clade during evolution.

No MeSH data available.