Chagas disease: a homology model for the three-dimensional structure of the Trypanosoma cruzi ribosomal P0 antigenic protein

Abstract

Ribosomal P proteins form a "stalk" complex in the large subunit of the ribosomes. In Trypanosoma cruzi, the etiological agent of Chagas disease, the complex is formed by five P protein members: TcP0, TcP1α, TcP1β, TcP2α and TcP2β. The TcP0 protein has 34 kDa, and TcP1 and TcP2 proteins have 10 kDa. The structure of T. cruzi P0 and the stalk complex TcP0-TcP1α-TcP1β-TcP2α-TcP2β have not been solved to date. In this work, we constructed a three-dimensional molecular model for TcP0 using homology modeling as implemented in the MODELLER 9v12 software. The model was constructed using different templates: the X-ray structures of the protein P0 from Pirococcus horikoshii, a segment from the Danio renio Ca(+2)/K(+) channel and the C-terminal peptide (C13) from T. cruzi ribosomal P2 protein; the Cryo-EM structure of Triticum aestivum P0 protein and the NMR structure of Homo sapiens P1 ribosomal protein. TcP0 has a 200-residue-long N-terminal, which is an α/β globular stable domain, and a flexible C-terminal, 120-residue-long domain. The molecular surface electrostatic potential and hydrophobic surface were calculated. The surface properties are important for the C-terminal's antigenic properties. They are also responsible for P0-specific binding to RNA26S and the binding to the P1-P2 proteins. We explored and identified protein interactions that may be involved in conformational stability. The structure proposed in this work represents a first structural report for the TcP0 protein.

Structure and function insights garnered from in silico modeling of the thrombospondin type‐1 domain‐containing 7A antigen

“…Taken together this work demonstrates an accurate prediction of epitope sites through the use of an in silico generated homology model of a very large antigen system. Homology models are quite often generated for much smaller systems . Typically when homology models are developed for large system it is in combination with cryo‐electron microscopy, and individual pieces of the model are fit into the larger overall surface map .…”

“…Homology models are quite often generated for much smaller systems. 20,[37][38][39] Typically when homology models are developed for large system it is in combination with cryo-electron microscopy, and individual pieces of the model are fit into the larger overall surface map. 4,40 In this work, even though we developed a very large scale homology model independently of cyro-electron microscopy data, the model proves to be useful for accurate prediction of epitope regions in THSD7A, as it is corroborated by the work of Seifert.…”

Detection of Human Anti-Trypanosoma cruzi Antibody with Recombinant Fragmented Ribosomal P Protein

“…Ribosomal P proteins form a complex of proteins in the large subunit of the ribosome that is called the stalk [9]. These proteins act as a molecular switch in the ribosome related to the binding and release of elongation factors and GTP hydrolysis [10].…”