title: Search for a platelet-activating factor receptor in the Trypanosoma cruzi proteome: a potential target for Chagas disease chemotherapy.
abstract: Chagas disease (CD) causes the highest burden of parasitic diseases in the Western Hemisphere and is therefore a priority for drug research and development. Platelet-activating factor (PAF) causes the CD parasite Trypanosoma cruzi to differentiate, which suggests that the parasite may express PAF receptors. Here, we explored the T. cruzi proteome for PAF receptor-like proteins. From a total of 23,000 protein sequences, we identified 29 hypothetical proteins that are predicted to have seven transmembrane domains (TMDs), which is the main characteristic of the G protein-coupled receptors (GPCRs), including the PAF receptor. The TMDs of these sequences were independently aligned with domains from 25 animal PAF receptors and the sequences were analysed for conserved residues. The conservation score mean values for the TMDs of the hypothetical proteins ranged from 31.7-44.1%, which suggests that if the putative T. cruzi PAF receptor is among the sequences identified, the TMDs are not highly conserved. These results suggest that T. cruzi contains several GPCR-like proteins and that one of these GPCRs may be a PAF receptor. Future studies may further validate the PAF receptor as a target for CD chemotherapy.
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brasil. dkawano@usp.br
authors.forename: Daniel Fábio
authors.initials: DF
authors.lastname: Kawano
authors.forename: Vinicius Barreto da
authors.initials: VB
authors.lastname: Silva
authors.forename: Daniel Macedo de Melo
authors.initials: DM
authors.lastname: Jorge
authors.forename: Carlos Henrique Tomich de Paula da
authors.initials: CH
authors.lastname: Silva
authors.forename: Ivone
authors.initials: I
authors.lastname: Carvalho
mesh_terms: D014355:Chagas Disease / Q000188:drug therapy; D019295:Computational Biology; D030562:Databases, Protein; D058990:Molecular Targeted Therapy; D010802:Phylogeny; D010980:Platelet Membrane Glycoproteins / Q000032:analysis*; D020543:Proteome / Q000737:chemistry*; D015800:Protozoan Proteins / Q000032:analysis*; D043562:Receptors, G-Protein-Coupled / Q000032:analysis*; D020539:Sequence Analysis, Protein; D014349:Trypanosoma cruzi / Q000737:chemistry*
chemical_list: D010980:Platelet Membrane Glycoproteins; D020543:Proteome; D015800:Protozoan Proteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor