Genome Survey Sequence Analysis and Identification of Homologs of Major Surface Protease (<i>gp63</i>) Genes in<i>Trypanosoma rangeli</i>

Ferreira, Keila Adriana Magalhães; Ruiz, Jerônimo C.; Dias, Fabrício C.; Lages‐Silva, Eliane; Tosi, Luiz Ricardo Orsini; Ramı́rez, Luı́s Eduardo; Pedrosa, André Luiz

doi:10.1089/vbz.2009.0128

Cited by 4 publications

References 26 publications

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GP63 Function in the Interaction of Trypanosomatids with the Invertebrate Host: Facts and Prospects

d’Avila-Levy

Altoé

Uehara

et al. 2013

Subcellular Biochemistry

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The GP63 of the protozoan parasite Leishmania is a highly abundant zinc metallopeptidase, mainly glycosylphosphatidylinositol-anchored to the parasite surface, which contributes to a myriad of well-established functions for Leishmania in the interaction with the mammalian host. However, the role of GP63 in the Leishmania-insect vector interplay is still a matter of controversy. Data from GP63 homologues in insect and plant trypanosomatids strongly suggest a participation of GP63 in this interface, either through nutrient acquisition or through binding to the insect gut receptors. GP63 has also been described in the developmental forms of Trypanosoma cruzi, Trypanosoma brucei and Trypanosoma rangeli that deal with the vector. Here, the available data from GP63 will be analyzed from the perspective of the interaction of trypanosomatids with the invertebrate host.

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GP63 Function in the Interaction of Trypanosomatids with the Invertebrate Host: Facts and Prospects

d’Avila-Levy

Altoé

Uehara

et al. 2013

Subcellular Biochemistry

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Species-specific markers for the differential diagnosis of Trypanosoma cruzi and Trypanosoma rangeli and polymorphisms detection in Trypanosoma rangeli

et al. 2014

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Trypanosoma cruzi and Trypanosoma rangeli are kinetoplastid parasites which are able to infect humans in Central and South America. Misdiagnosis between these trypanosomes can be avoided by targeting barcoding sequences or genes of each organism. This work aims to analyze the feasibility of using species-specific markers for identification of intraspecific polymorphisms and as target for diagnostic methods by PCR. Accordingly, primers which are able to specifically detect T. cruzi or T. rangeli genomic DNA were characterized. The use of intergenic regions, generally divergent in the trypanosomatids, and the serine carboxypeptidase gene were successful. Using T. rangeli genomic sequences for the identification of group-specific polymorphisms and a polymorphic AT(n) dinucleotide repeat permitted the classification of the strains into two groups, which are entirely coincident with T. rangeli main lineages, KP1 (+) and KP1 (-), previously determined by kinetoplast DNA (kDNA) characterization. The sequences analyzed totalize 622 bp (382 bp represent a hypothetical protein sequence, and 240 bp represent an anonymous sequence), and of these, 581 (93.3%) are conserved sites and 41 bp (6.7%) are polymorphic, with 9 transitions (21.9%), 2 transversions (4.9%), and 30 (73.2%) insertion/deletion events. Taken together, the species-specific markers analyzed may be useful for the development of new strategies for the accurate diagnosis of infections. Furthermore, the identification of T. rangeli polymorphisms has a direct impact in the understanding of the population structure of this parasite.

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Gene identification and comparative molecular modeling of a Trypanosoma rangeli major surface protease

et al. 2013

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Trypanosoma rangeli is a hemoflagellate parasite which is able to infect humans. Distinct from Trypanosoma cruzi, the causative agent of Chagas disease, T. rangeli is non-pathogenic to the vertebrate host. The manner by which the T. rangeli interacts with the host is still unknown, but it certainly depends on the surface molecules. Major surface proteins (MSP) are GPI-anchored, zinc-dependent metalloproteases present in the surface of all trypanosomatids studied so far, which are implicated as virulence factors in pathogenic trypanosomatids, such as Leishmania spp and T. cruzi. The aims of this work were to generate the complete sequence of a T. rangeli MSP (TrMSP) gene and to determine the 3D-structure of the predicted protein by homology modeling. The plasmid bearing a complete copy of a TrMSP gene was completely sequenced and the predicted protein was modeled using Modeller software. Results indicate that TrMSP open reading frame (ORF) codes for a predicted 588 amino acid protein and shows all elements required for its posttranslational processing. Multiple sequence alignment of TrMSP with other trypanosomatids' MSPs showed an extensive conservation of the N-terminal and central regions and a more divergent C-terminal region. Leishmania major MSP (LmMSP), which had its crystal structure previously determined, has an overall 35% identity with TrMSP. This identity allowed the comparative molecular modeling of TrMSP, which demonstrated a high degree of structural conservation between MSPs from other trypanosomatids (TrypMSPs). All modeled MSPs have a conserved folding pattern, apart from structural divergences in the C-domain and discrete differences of charge and topology in the catalytic cleft, and present the same geometry of the canonical HEXXH zinc-binding motif. The determination of surface charges of the molecules revealed that TrMSP is a predominantly positive protein, whereas LmMSP and Trypanosoma cruzi MSP (TcMSP) are negative proteins, suggesting that substrates recognized by TcMSP and LmMSP could not interact with TrMSP. Moreover, the comparison between TrMSP and TcMSP protein sequences has revealed 45 non-neutral amino acid substitutions, which can be further assessed through protein engineering. The characteristics of TrMSP could explain, at least in part, the lack of pathogenicity of T. rangeli to humans and point to the necessity of identifying the biological targets of this enzyme.

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Genome Survey Sequence Analysis and Identification of Homologs of Major Surface Protease (gp63) Genes inTrypanosoma rangeli

Cited by 4 publications

References 26 publications

GP63 Function in the Interaction of Trypanosomatids with the Invertebrate Host: Facts and Prospects

GP63 Function in the Interaction of Trypanosomatids with the Invertebrate Host: Facts and Prospects

Species-specific markers for the differential diagnosis of Trypanosoma cruzi and Trypanosoma rangeli and polymorphisms detection in Trypanosoma rangeli

Gene identification and comparative molecular modeling of a Trypanosoma rangeli major surface protease

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