In silico integrative analysis for the characterization of LYT1 a unique protein of Trypanosoma cruzi

Abstract

Trypanosoma rangeli is the most similar organism to Trypanosoma cruzi. They share distribution areas, hosts, and some vectors. However, there are key differences between them; the first lacks a multiplicative form in the host and does not cause disease, while the second is the etiological agent of the American tripanosomiasis, a tropical disease that still does not have an effective vaccine nor treatment. Aiming to reveal the differences in their gene expression patterns in each life cycle form, the comparison of expression profiles was made parting from the ESTs available in TriTrypDB. We verified that there are no genes unique to T. rangeli in the ESTs. Astonishingly, we determined that T. cruzi has a single copy gene called LYT1, which has no similarity to any other protein of any organism on Earth. LYT1 is involved in invasion, motility, and cell cycle, making it an attractive vaccine target. After its identification, using immunoinformatics programs, we found multiple potential B- and T-cell epitopes in this protein, which is also rich in intrinsically disordered regions. Additionally, an approximation of the 3 D structure was predicted where the B-cell epitopes were located to assess their solvent access. We propose that its particular structural conformation confers the flexibility required for the interactions with multiple proteins, which in part may be performed through N-myristoylation sites. Given its important role in the infectiveness of T. cruzi and its antigenic potential, we highlight the need for future studies focused on its molecular and immunological in vivo characterization. Communicated by Ramaswamy H. Sarma