Metals and metalloids as binding antigens in a new variant of endemic pemphigus in El Bagre, Colombia, South America

Abstract

We have previously described an autoimmune orphan disease, a new variant of endemic pemphigus in El Bagre, Colombia. The disease is present in a geological area most rich in polluting metals and metalloids and specifically contaminated by mercury and cyanide widely used for gold and other metals mining. Our aim was to identify potential metal-binding sequences in the canonical antigenic proteins of this disease. We performed a thorough web search for putative metal binding sites in the canonical antigenic proteins of the desmoglein familyusing the machine learning-based methodmebipred and the UniProtKB/Swiss-Prot (UniProt), Uniprot.org and the Protein Data Base (PDB). We have found that basically all of these antigens may possess metal binding sites (p<0.05): Desmoglein 1 (Ca, Zn, 2Fe-2S, 3Fe-4S, 4Fe-4S sites); Desmoplakin (Ca, Mg, Zn, Fe binding sites); Myocardium-enriched zonula occlusans-1 associated protein (K, Mg binding sites); Armadillo Repeat Protein deleted in velo-cardio-facial syndrome (Ca, Co, Fe, Ni, Zn binding sites); envoplakin (Co, Mg, K, Mn, K, Ni, Zn binding sites); periplakin (Ca, Mg, Mn, Ni binding sites); Bullous pemphigoid antigen 2 (BP230) (Co, Mg, Mn, Ni, Zn binding sites); plakophilin-4 (Co, Mg, Mn, Na binding sites).The FASTA sequences for all known antigens for people affected by endemic pemphigus in El Bagre have putative metal binding sites. Experimental studies of these proteins are needed to confirm these predictions.