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Surface antigens and potential virulence factors from parasites detected by comparative genomics of perfect amino acid repeats.

Fankhauser N, Nguyen-Ha TM, Adler J, Mäser P - Proteome Sci (2007)

Bottom Line: They find immunological applications in serodiagnostics and vaccine development.Reptile combined with programs for the prediction of transmembrane domains and GPI-anchoring resulted in an effective tool for in silico identification of potential surface antigens and virulence factors from parasites.Systemic surveys for perfect amino acid repeats allowed basic comparisons between free-living and parasitic organisms that were directly applicable to predict proteins of serological and parasitological importance.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Bern, Institute of Cell Biology, Baltzerstrasse 4, CH-3012 Bern, Switzerland. pascal.maeser@izb.unibe.ch.

ABSTRACT

Background: Many parasitic organisms, eukaryotes as well as bacteria, possess surface antigens with amino acid repeats. Making up the interface between host and pathogen such repetitive proteins may be virulence factors involved in immune evasion or cytoadherence. They find immunological applications in serodiagnostics and vaccine development. Here we use proteins which contain perfect repeats as a basis for comparative genomics between parasitic and free-living organisms.

Results: We have developed Reptile http://reptile.unibe.ch, a program for proteome-wide probabilistic description of perfect repeats in proteins. Parasite proteomes exhibited a large variance regarding the proportion of repeat-containing proteins. Interestingly, there was a good correlation between the percentage of highly repetitive proteins and mean protein length in parasite proteomes, but not at all in the proteomes of free-living eukaryotes. Reptile combined with programs for the prediction of transmembrane domains and GPI-anchoring resulted in an effective tool for in silico identification of potential surface antigens and virulence factors from parasites.

Conclusion: Systemic surveys for perfect amino acid repeats allowed basic comparisons between free-living and parasitic organisms that were directly applicable to predict proteins of serological and parasitological importance. An on-line tool is available at http://genomics.unibe.ch/dora.

No MeSH data available.


Flowchart to Dora, database of repetitive antigens. Reptile, Phobius [20], and GPI-SOM [43] are integrated into an automated pipeline for the classification of proteins (top). The data are stored in a database that is accessible on-line [44] via the depicted interface (bottom). This allows user-defined Boolean queries for repeat-containing surface proteins.
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Figure 4: Flowchart to Dora, database of repetitive antigens. Reptile, Phobius [20], and GPI-SOM [43] are integrated into an automated pipeline for the classification of proteins (top). The data are stored in a database that is accessible on-line [44] via the depicted interface (bottom). This allows user-defined Boolean queries for repeat-containing surface proteins.

Mentions: In order to predict which of the repeat-containing proteins are at the cell surface, Reptile was combined with Phobius [42], a program for prediction of transmembrane domains and N-terminal export signals, and GPI-SOM [43], a program that predicts C-terminal GPI (glycosylphosphatidyl-inositol) anchor attachment sites. The three programs were run over all available proteomes predicted from completely sequenced genomes. The identified repeats were scanned for potential N-glycosylation sites. The combined output was stored in a relational database called Dora, the database of repetitive antigens, as outlined in Figure 4. At present, Dora contains data on 1,123,238 proteins from 242 different proteomes (among which 49 eukaryotic). A www interface [44] allows user-defined Boolean searches (Figure 4). With Dora, genome-wide prediction of potential surface antigens and virulence factors is straightforward. A search for repetitive membrane proteins in P. falciparum or T. brucei (Table 4) indeed returned important surface antigens and virulence factors: circumsporozoite protein (CSP), merozoite surface proteins (MSP), erythrocyte membrane proteins (EMP), glycophorin-binding proteins (GBP), apical membrane/erythrocyte binding antigen (MAEBL), ring-infected erythrocyte surface antigen (RESA), mature parasite-infected erythrocyte surface antigen (MESA) for malaria and for T. brucei the procyclins, cysteine-rich acidic membrane protein (CRAM), invariant surface glycoproteins (ISG) and even the variable surface glycoproteins (VSG), which contain a significant number of dipeptide repeats (mostly AA; to our knowledge the repetitive nature of VSG was not previously recognized). In addition to these known proteins there was a large number of uncharacterized ones, particularly from P. falciparum which possesses hundreds of extremely repetitive transmembrane proteins (not shown; please refer to Dora).


Surface antigens and potential virulence factors from parasites detected by comparative genomics of perfect amino acid repeats.

Fankhauser N, Nguyen-Ha TM, Adler J, Mäser P - Proteome Sci (2007)

Flowchart to Dora, database of repetitive antigens. Reptile, Phobius [20], and GPI-SOM [43] are integrated into an automated pipeline for the classification of proteins (top). The data are stored in a database that is accessible on-line [44] via the depicted interface (bottom). This allows user-defined Boolean queries for repeat-containing surface proteins.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2254594&req=5

Figure 4: Flowchart to Dora, database of repetitive antigens. Reptile, Phobius [20], and GPI-SOM [43] are integrated into an automated pipeline for the classification of proteins (top). The data are stored in a database that is accessible on-line [44] via the depicted interface (bottom). This allows user-defined Boolean queries for repeat-containing surface proteins.
Mentions: In order to predict which of the repeat-containing proteins are at the cell surface, Reptile was combined with Phobius [42], a program for prediction of transmembrane domains and N-terminal export signals, and GPI-SOM [43], a program that predicts C-terminal GPI (glycosylphosphatidyl-inositol) anchor attachment sites. The three programs were run over all available proteomes predicted from completely sequenced genomes. The identified repeats were scanned for potential N-glycosylation sites. The combined output was stored in a relational database called Dora, the database of repetitive antigens, as outlined in Figure 4. At present, Dora contains data on 1,123,238 proteins from 242 different proteomes (among which 49 eukaryotic). A www interface [44] allows user-defined Boolean searches (Figure 4). With Dora, genome-wide prediction of potential surface antigens and virulence factors is straightforward. A search for repetitive membrane proteins in P. falciparum or T. brucei (Table 4) indeed returned important surface antigens and virulence factors: circumsporozoite protein (CSP), merozoite surface proteins (MSP), erythrocyte membrane proteins (EMP), glycophorin-binding proteins (GBP), apical membrane/erythrocyte binding antigen (MAEBL), ring-infected erythrocyte surface antigen (RESA), mature parasite-infected erythrocyte surface antigen (MESA) for malaria and for T. brucei the procyclins, cysteine-rich acidic membrane protein (CRAM), invariant surface glycoproteins (ISG) and even the variable surface glycoproteins (VSG), which contain a significant number of dipeptide repeats (mostly AA; to our knowledge the repetitive nature of VSG was not previously recognized). In addition to these known proteins there was a large number of uncharacterized ones, particularly from P. falciparum which possesses hundreds of extremely repetitive transmembrane proteins (not shown; please refer to Dora).

Bottom Line: They find immunological applications in serodiagnostics and vaccine development.Reptile combined with programs for the prediction of transmembrane domains and GPI-anchoring resulted in an effective tool for in silico identification of potential surface antigens and virulence factors from parasites.Systemic surveys for perfect amino acid repeats allowed basic comparisons between free-living and parasitic organisms that were directly applicable to predict proteins of serological and parasitological importance.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Bern, Institute of Cell Biology, Baltzerstrasse 4, CH-3012 Bern, Switzerland. pascal.maeser@izb.unibe.ch.

ABSTRACT

Background: Many parasitic organisms, eukaryotes as well as bacteria, possess surface antigens with amino acid repeats. Making up the interface between host and pathogen such repetitive proteins may be virulence factors involved in immune evasion or cytoadherence. They find immunological applications in serodiagnostics and vaccine development. Here we use proteins which contain perfect repeats as a basis for comparative genomics between parasitic and free-living organisms.

Results: We have developed Reptile http://reptile.unibe.ch, a program for proteome-wide probabilistic description of perfect repeats in proteins. Parasite proteomes exhibited a large variance regarding the proportion of repeat-containing proteins. Interestingly, there was a good correlation between the percentage of highly repetitive proteins and mean protein length in parasite proteomes, but not at all in the proteomes of free-living eukaryotes. Reptile combined with programs for the prediction of transmembrane domains and GPI-anchoring resulted in an effective tool for in silico identification of potential surface antigens and virulence factors from parasites.

Conclusion: Systemic surveys for perfect amino acid repeats allowed basic comparisons between free-living and parasitic organisms that were directly applicable to predict proteins of serological and parasitological importance. An on-line tool is available at http://genomics.unibe.ch/dora.

No MeSH data available.