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In silico analysis of the cyclophilin repertoire of apicomplexan parasites.

Krücken J, Greif G, von Samson-Himmelstjerna G - Parasit Vectors (2009)

Bottom Line: In addition, cyclosporine is known to exhibit anti-parasitic effects on a wide range of organisms including several apicomplexa.In order to obtain new non-immunosuppressive drugs targeting apicomplexan cyclophilins, a profound knowledge of the cyclophilin repertoire of this phylum would be necessary.The genomes of apicomplexa harbor a cyclophilin repertoire that is at least as complex as that of most fungi.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Parasitology, University of Veterinary Medicine Foundation, Bünteweg 17, 30559 Hannover, Germany. juergen.kruecken@tiho-hannover.de.

ABSTRACT

Background: Cyclophilins (Cyps) are peptidyl cis/trans isomerases implicated in diverse processes such as protein folding, signal transduction, and RNA processing. They are also candidate drug targets, in particular for the immunosuppressant cyclosporine A. In addition, cyclosporine is known to exhibit anti-parasitic effects on a wide range of organisms including several apicomplexa. In order to obtain new non-immunosuppressive drugs targeting apicomplexan cyclophilins, a profound knowledge of the cyclophilin repertoire of this phylum would be necessary.

Results: BLAST and maximum likelihood analyses identified 16 different cyclophilin subfamilies within the genomes of Cryptosporidium hominis, Toxoplasma gondii, Plasmodium falciparum, Theileria annulata, Theileria parva, and Babesia bovis. In addition to good statistical support from the phylogenetic analysis, these subfamilies are also confirmed by comparison of cyclophilin domain architecture. Within an individual genome, the number of different Cyp genes that could be deduced varies between 7-9 for Cryptosporidia and 14 for T. gondii. Many of the putative apicomplexan cyclophilins are predicted to be nuclear proteins, most of them presumably involved in RNA processing.

Conclusion: The genomes of apicomplexa harbor a cyclophilin repertoire that is at least as complex as that of most fungi. The identification of Cyp subfamilies that are specific for lower eukaryotes, apicomplexa, or even the genus Plasmodium is of particular interest since these subfamilies are not present in host cells and might therefore represent attractive drug targets.

No MeSH data available.


PPIA-like Cyps with signal peptide. Domain architecture and genomic organization of Cyps with signal peptide are shown. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); SP, signal peptide.
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Figure 3: PPIA-like Cyps with signal peptide. Domain architecture and genomic organization of Cyps with signal peptide are shown. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); SP, signal peptide.

Mentions: The dendrogram in Figure 1 reveals a group of putative small Cyps with SP that also contain a Cyp_ABH type domain and are relatively closely related to the PPIA-type Cyps. The domain architecture and genomic organization of these Cyps is schematically presented in Figure 3. One putative member of this Cyp subfamily could be identified in each apicomplexan genome. In contrast to the small cytosolic PPIA-like Cyps, the coding regions of all subfamily members are interrupted by introns. Whereas C. hominis and T. gondii show a very similar exon/intron structure with 4 introns, the putative genes of both Theileria species have only 2 introns – apparently due to fusion of exons 3 and 4 – and after further fusion of exons 1 and 2 only a single intron remains in B. bovis. In PfCyp21.7, loss of introns has resulted in a Cyp domain that is encoded by a single exon. However, a new intron has also appeared within the region encoding the SP, which is encoded by a single exon in the other Cyps of this subfamily.


In silico analysis of the cyclophilin repertoire of apicomplexan parasites.

Krücken J, Greif G, von Samson-Himmelstjerna G - Parasit Vectors (2009)

PPIA-like Cyps with signal peptide. Domain architecture and genomic organization of Cyps with signal peptide are shown. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); SP, signal peptide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2713222&req=5

Figure 3: PPIA-like Cyps with signal peptide. Domain architecture and genomic organization of Cyps with signal peptide are shown. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); SP, signal peptide.
Mentions: The dendrogram in Figure 1 reveals a group of putative small Cyps with SP that also contain a Cyp_ABH type domain and are relatively closely related to the PPIA-type Cyps. The domain architecture and genomic organization of these Cyps is schematically presented in Figure 3. One putative member of this Cyp subfamily could be identified in each apicomplexan genome. In contrast to the small cytosolic PPIA-like Cyps, the coding regions of all subfamily members are interrupted by introns. Whereas C. hominis and T. gondii show a very similar exon/intron structure with 4 introns, the putative genes of both Theileria species have only 2 introns – apparently due to fusion of exons 3 and 4 – and after further fusion of exons 1 and 2 only a single intron remains in B. bovis. In PfCyp21.7, loss of introns has resulted in a Cyp domain that is encoded by a single exon. However, a new intron has also appeared within the region encoding the SP, which is encoded by a single exon in the other Cyps of this subfamily.

Bottom Line: In addition, cyclosporine is known to exhibit anti-parasitic effects on a wide range of organisms including several apicomplexa.In order to obtain new non-immunosuppressive drugs targeting apicomplexan cyclophilins, a profound knowledge of the cyclophilin repertoire of this phylum would be necessary.The genomes of apicomplexa harbor a cyclophilin repertoire that is at least as complex as that of most fungi.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Parasitology, University of Veterinary Medicine Foundation, Bünteweg 17, 30559 Hannover, Germany. juergen.kruecken@tiho-hannover.de.

ABSTRACT

Background: Cyclophilins (Cyps) are peptidyl cis/trans isomerases implicated in diverse processes such as protein folding, signal transduction, and RNA processing. They are also candidate drug targets, in particular for the immunosuppressant cyclosporine A. In addition, cyclosporine is known to exhibit anti-parasitic effects on a wide range of organisms including several apicomplexa. In order to obtain new non-immunosuppressive drugs targeting apicomplexan cyclophilins, a profound knowledge of the cyclophilin repertoire of this phylum would be necessary.

Results: BLAST and maximum likelihood analyses identified 16 different cyclophilin subfamilies within the genomes of Cryptosporidium hominis, Toxoplasma gondii, Plasmodium falciparum, Theileria annulata, Theileria parva, and Babesia bovis. In addition to good statistical support from the phylogenetic analysis, these subfamilies are also confirmed by comparison of cyclophilin domain architecture. Within an individual genome, the number of different Cyp genes that could be deduced varies between 7-9 for Cryptosporidia and 14 for T. gondii. Many of the putative apicomplexan cyclophilins are predicted to be nuclear proteins, most of them presumably involved in RNA processing.

Conclusion: The genomes of apicomplexa harbor a cyclophilin repertoire that is at least as complex as that of most fungi. The identification of Cyp subfamilies that are specific for lower eukaryotes, apicomplexa, or even the genus Plasmodium is of particular interest since these subfamilies are not present in host cells and might therefore represent attractive drug targets.

No MeSH data available.