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|Title: ||Searching for new clues about the molecular cause of endomyocardial fibrosis by way of in SilicoProteomics and analytical chemistry|
|Authors: ||Wayengera, Misaki|
|Issue Date: ||2009 |
|Publisher: ||Public Library of Science|
|Citation: ||Wayengera, M. (2009). Searching for New Clues about the Molecular Cause of Endomyocardial Fibrosis by Way of In Silico Proteomics and Analytical Chemistry. PLoS ONE 4(10): e7420.|
|Abstract: ||Background: Endomyocardial Fibrosis (EMF) –is a chronic inflammatory disease of the heart with related pathology to that of late stage Chaga’s disease. Indeed, both diseases are thought to result from auto-immune responses against myocardial tissue. As is the case that molecular mimicry between the acidic termini of Trypanosoma cruzi ribosomal P0, P1 and P2b (or simply TcP0, TcP1, and TcP2b) proteins and myocardial tissue causes Chaga’s disease, excessive exposure to certain infections, toxins including cassava ones, allergy and malnutrition has been suggested as the possible cause for EMF. Recent studies have defined the proteomic characteristics of the T. cruzi ribosomal P protein-C-termini involved in mediating autoimmunity against Beta1-adrenergic receptors of the heart in Chaga’s disease. This study aimed to investigate the similarity of C-termini of TcP0/TcP2b to sequences and molecules of several plants, microbial, viral and chemical elements- most prior thought to be possible causative agents for EMF.
Methods and Principal Findings: Comparative Sequence alignments and phylogeny using the BLAST-P tool at the Swiss Institute of Biotechnology (SIB) revealed homologs of C-termini of TcP0 and TcP2b among related proteins from several eukaryotes including the animals (Homo sapiens, C. elegans, D. melanogaster), plants (Arabidopsis thaliana, Zea mays, Glycina Max, Oryza sativa, Rhizopus oryzae) and protozoa (P. falciparum, T. gondii, Leishmania spp). The chemical formulae of the two T.cruzi ribosomal protein C-terminal peptides were found to be C61H83N13O26S1 and C64H87N13O28S1 respectively by Protparam. Both peptides are heavily negatively charged. Constitutively, both auto-antigens predominantly contain Asparagine (D), Glycine (G) and Phenylamine (F), with a balanced Leucine (L) and Methionine (M) percent composition of 7.7%. The afore going composition, found to be non-homologous to all molecules of chemical species in the databases searched, suggests the possible role of a metabolic pathway in the pathogenesis of EMF if aligned with our ‘‘molecular mimicry’’ hypothesis.
Conclusions: Our findings provide a ‘‘window’’ to suggest that cross reactivity of antibodies against C-terminal sequences of several animal, plant and protozoal ribosomal P proteins with heart tissue may mediate EMF in a similar manner as Ctermini of T. cruzi do for Chaga’s disease.|
|Description: ||This article is available from http://dx.doi.org/10.1371/journal.pone.0007420|
|Appears in Collections:||Research Articles (Health-Sciences)|
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