RESUMO
Proteins containing repetitive amino acid domains are widespread in all life forms. In parasitic organisms, proteins containing repeats play important roles such as cell adhesion and invasion and immune evasion. Therefore, extracellular and intracellular parasites are expected to be under different selective pressures regarding the repetitive content in their genomes. Here, we investigated whether there is a bias in the repetitive content found in the predicted proteomes of 6 exclusively extracellular and 17 obligate intracellular protozoan parasites, as well as 4 free-living protists. We also attempted to correlate the results with the distinct ecological niches they occupy and with distinct protein functions. We found that intracellular parasites have higher repetitive content in their proteomes than do extracellular parasites and free-living protists. In intracellular parasites, these repetitive proteins are located mainly at the parasite surface or are secreted and are enriched in amino acids known to be part of N- and O-glycosylation sites. Furthermore, in intracellular parasites, the developmental stages that are able to invade host cells express a higher proportion of proteins with perfect repeats relative to other life cycle stages, and these proteins have molecular functions associated with cell invasion. In contrast, in extracellular parasites, degenerate repetitive motifs are enriched in proteins that are likely to play roles in evading host immune response. Altogether, our results support the hypothesis that both the ability to invade host cells and to escape the host immune response may have shaped the expansion and maintenance of perfect and degenerate repeats in the genomes of intra- and extracellular parasites.
Assuntos
Alveolados/genética , Amebozoários/genética , Diplomonadida/genética , Proteínas de Protozoários/genética , Trypanosomatina/genética , Alveolados/imunologia , Amebozoários/imunologia , Animais , Diplomonadida/imunologia , Interações Hospedeiro-Parasita , Humanos , Evasão da Resposta Imune/genética , Processamento de Proteína Pós-Traducional , Proteoma/química , Proteoma/genética , Proteoma/metabolismo , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Sequências Repetitivas de Aminoácidos , Trypanosomatina/imunologiaRESUMO
The translationally controlled tumor protein (TCTP) is conserved in all eukaryotes studied thus far. Recent evidence points to an important role for TCTP in the induction of cell proliferation in animals through an interaction with G proteins. TCTP may also constitute an intercellular secreted signal that modulates the immune response in the vertebrates. Because of its sequence conservation and ubiquity, the analysis of its amino acid sequence divergence between different taxa may provide insight into the structural constraints on the evolution of this protein. In the present study, we analyzed the phylogeny of TCTP sequences from a wide range of organisms and found that, with some exceptions, the groupings formed were consistent with the evolutionary history. Indeed, at the level of lower-order taxa, the groupings are in agreement with their established phylogeny, thus indicating that the substitution rates of the TCTP residues varied evenly between members of the same clade. Predicted three-dimensional structures of representative TCTPs, based on the reported 3D structure of Schizosaccharomyces pombe, indicated that these proteins are highly conserved among diverse taxonomic groups. However, analysis of the primary structure indicated subtle differences in the domain-forming pocket that potentially interacts with G proteins, particularly among Diplomonadidae, Apicomplexa, and other parasites of vertebrates. These differences support the notion that these specific TCTPs could block the normal immune response by acting as dominant negative mutants. Structural differences were also observed in a reported sequence of TCTP from Plasmodium knowlesi, in which the presence of an extra alpha-helix could also interfere in the interaction with G proteins.