Chagas´s Disease: Conformational study of immunopeptides

MARTÍN, OSVALDO; VILLEGAS, MYRIAM; AGUILAR, CARLOS

Rosario, Santa Fe

Congreso; XXXV Reunión Anual de la Sociedad Argentina de Biofísica; 2006

Sociedad Argentina de Biofísica

The Chagas`s disease or American Trypanosomiasis is a parasitosis produced by the flagellated protozoa Trypanosoma cruzi. The overall prevalence of the infection is estimated at 16-18 million cases. Chronic Chagas´s heart disease (cChHD) is a myocarditis characterized by arrhythmia, tachycardia and heart failure. In the chronic phase of the disease patients present antibodies against the conserved acidic C-terminal of T. cruzi ribosomal P proteins. Ribosomal P proteins form a complex which constitute the stalk, a long and protruding region, on the large subunit. The T. cruzi`s stalk is formed by P0, P1(alpha), P1(beta) P2(alpha) and P2(beta). It has been proposed that cChHD is an autoimmune disease produced by molecular mimicry between the ribosomal P proteins C-terminal and the second extracelular loop of the (beta)1-adrenoreceptor, denominated H26R. The active immunization with P0 and P2(beta) recombinant proteins from T. cruzi has been shown to induce stimulation of the (beta)1-adrenoeceptor in murine models. Another research has associated the dysfunction of the retina, suffered by chagasic patients, with a similar autoimmune mechanism in which anti-P auto-antibodies would cross-react with the visual pigment rhodopsin. The aim of this work is to contribute to the understanding of the molecular basis of the autoimmune disease; correlating the available experimental data with models obtained using molecular simulation with Electrostatically Driven MonteCarlo. ECEPP/3 force field and different models for solvent interaction. Models of R13: EEEDDDMGFGLFD, P013: EDDDDDFGMGALF (corresponding to the last 13 aminoacids of T. cruzi´s P2(beta) and P0 respectively), and H26R: HWWRAESDEARRCYNDPKCCDFVTNR were compared with the experimental NMR structure of H13: EESDDDMGFGLFD (P0 human protein) and the crystallographic structure of rhodopsin. The antigen-antibody interaction was analyzed through docking these peptides onto the target antibody, the homology model of the monoclonal antibody anti-P2(beta) (mAb17).