title: 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.
authors.affiliation: Laboratorio de Biología Molecular Estructural; Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina, jagomez@unsl.edu.ar.
authors.forename: Juan Arturo
authors.initials: JA
authors.lastname: Gomez Barroso
authors.forename: Carlos Fernando
authors.initials: CF
authors.lastname: Aguilar
mesh_terms: D014355:Chagas Disease / Q000469:parasitology*; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry*; D012269:Ribosomal Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D013499:Surface Properties; D014349:Trypanosoma cruzi / Q000502:physiology*
chemical_list: D015800:Protozoan Proteins; D012269:Ribosomal Proteins; C054675:ribosomal protein P0