Limits...
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.


CeCyp16-like Cyps. Domain architecture and genomic organization of CeCyp16-like Cyps. Species are abbreviated as in Fig. 1. Cyp_CeCyp16, CeCyp16-type Cyp domain (CD accession-no: [cd01925]); NLS, nuclear localization signal; coiled-coil, coiled-coil protein interaction region; RR, Arg-rich region; KR, Lys-rich region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2713222&req=5

Figure 13: CeCyp16-like Cyps. Domain architecture and genomic organization of CeCyp16-like Cyps. Species are abbreviated as in Fig. 1. Cyp_CeCyp16, CeCyp16-type Cyp domain (CD accession-no: [cd01925]); NLS, nuclear localization signal; coiled-coil, coiled-coil protein interaction region; RR, Arg-rich region; KR, Lys-rich region.

Mentions: In contrast to most other moderate to large size Cyps, the subfamily containing a Cyp-CeCyp16-like domain (accession number: [cd01925]) does not contain any additional domain that could be identified by CD-BLAST or InterProScan (Figure 13). However, there is a nuclear localization signal detectable in all putative apicomplexan CeCyp16-like Cyps, which is located in approximately the same distance from the Cyp domain in all subfamily members with the exception of TgCyp64.5 where it immediately follows the Cyp domain. Moreover, using PSORTII at least one coiled-coil protein-protein interaction domain can be identified in all these proteins but CmCyp43.1 (for CmCyp43.1 the score for a coiled-coil region is only slightly too small to be judged as significant by PSORTII). PfCyp51.8 is even predicted to contain two coiled-coil regions. Moreover, PfCyp51.8 has a large Lys-rich region encompassing both coiled-coil domains. A comparable but much smaller positively charged region consisting of a large number of Arg residues is present in TgCyp64.5.


In silico analysis of the cyclophilin repertoire of apicomplexan parasites.

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

CeCyp16-like Cyps. Domain architecture and genomic organization of CeCyp16-like Cyps. Species are abbreviated as in Fig. 1. Cyp_CeCyp16, CeCyp16-type Cyp domain (CD accession-no: [cd01925]); NLS, nuclear localization signal; coiled-coil, coiled-coil protein interaction region; RR, Arg-rich region; KR, Lys-rich region.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 13: CeCyp16-like Cyps. Domain architecture and genomic organization of CeCyp16-like Cyps. Species are abbreviated as in Fig. 1. Cyp_CeCyp16, CeCyp16-type Cyp domain (CD accession-no: [cd01925]); NLS, nuclear localization signal; coiled-coil, coiled-coil protein interaction region; RR, Arg-rich region; KR, Lys-rich region.
Mentions: In contrast to most other moderate to large size Cyps, the subfamily containing a Cyp-CeCyp16-like domain (accession number: [cd01925]) does not contain any additional domain that could be identified by CD-BLAST or InterProScan (Figure 13). However, there is a nuclear localization signal detectable in all putative apicomplexan CeCyp16-like Cyps, which is located in approximately the same distance from the Cyp domain in all subfamily members with the exception of TgCyp64.5 where it immediately follows the Cyp domain. Moreover, using PSORTII at least one coiled-coil protein-protein interaction domain can be identified in all these proteins but CmCyp43.1 (for CmCyp43.1 the score for a coiled-coil region is only slightly too small to be judged as significant by PSORTII). PfCyp51.8 is even predicted to contain two coiled-coil regions. Moreover, PfCyp51.8 has a large Lys-rich region encompassing both coiled-coil domains. A comparable but much smaller positively charged region consisting of a large number of Arg residues is present in TgCyp64.5.

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.