Structural characteristics of the Trypanosoma cruzi ribosomal P0 protein have a major role in the induction of pathogenic antibodies in Chagas disease

CRISTIAN SMULSKI; MARTÍN EDREIRA; MAXIMILIANO JURI AYUB; PABLO LÓPEZ BERGAMI; CARLOS AGUILAR; MARIANO LEVIN

Villa Carlos Paz, Córdoba, Argentina.

Congreso; XXXVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2002

In human and murine infection with T. cruzi, humoral response against the ribosomal P proteins (P0, P1, P2a and P2b) is directed to the C-terminal regions, and for P0 it is exclusively directed to the C-terminal epitope P015. In contrast immunization with recombinant MBP-P0 induced antibodies against the whole protein, indicating the presence of antigenic sites others than the C-terminal epitope. Evidences collected from biophysical determinations, limited proteolysis assays and mapping with sera and monoclonal antibodies, allowed to propose that P0 presents a highly flexible, unstructured C-terminal domain, fused through an exposed loop to a large globular N-terminal domain. Thus, in the infection the central and the N-terminal epitopes of P0 would be hidden into the compact tertiary structure. In contrast, immunization with an unfolded recombinant P0 protein would allow the presentation of hidden epitopes. Using yeast two hybrid assay we demonstrated the physical interaction between P0 and P1. The inclusion of P0, through its interaction with P1, in the P protein pentameric complex that forms the T. cruzi ribosome stalk, highlights the relevance of the flexibility and exposure of the C-terminal end of P0 in inducing an humoral response during infection.