Post translational Modifications and Protein-Protein Interactome of Endemic Pemphigus in El Bagre, Colombia: A New Variant Analysis.

Introduction: A new variant of endemic pemphigus foliaceus, El Bagre-EPF, is an orphan autoimmune disease occurring in El Bagre and neighboring municipalities in Colombia, South America.

Objectives: We aimed to evaluate current state-of-the-art databases and protein-protein interactomes, focusing on post-translational modifications as potential tools to study interactions among El Bagre-EPF antigen proteins.

Methods: We consulted multiple databases for the known target antigens and their protein-protein interactions. We searched for their network nodes (they represent proteins; each node corresponded to all the proteins produced by a single, protein-coding gene locus). We also searched for any post-translational modifications.

Results: We identified similarities in proteins bound by several autoantigens but also found differences in protein linkages. We found that desmoglein, periplakin, desmoplakins, and proteins from subfamilies of the Armadillo repeat proteins and some spectrin domains linked to other cell junctions; these played important roles in membrane-plaque and intermediate filament junctions. A typical drawback in current databases is the lack of information on lipid-protein interactions.

Conclusions: Our results show that state-of-the-art protein databases as tools for studies of interactomes fall short in areas including tertiary and quaternary protein interactions and in vivo protein functioning. Enhanced three-dimensional or multi-dimensional functions are required for more accurate interactome analyses.