Transglutaminases in Dysbiosis As Potential Environmental Drivers of Autoimmunity.

Aaron Lerner,Rustam Aminov,Torsten Matthias

doi:10.3389/fmicb.2017.00066

Abstract

Protein-glutamine γ-glutamyltransferases (transglutaminases, Tgs) belong to the class of transferases. They catalyze the formation of an isopeptide bond between the acyl group at the end of the side chain of protein- or peptide-bound glutamine residues and the first order 𝜀-amine groups of protein- or peptide-bound lysine. The Tgs are considered to be universal protein cross-linkers, and they play an essential role in a number of human diseases. In this review, we discuss mainly the bacterial Tgs in terms of the functionality of the enzymes and a potential role they may play in bacterial survival. Since microbial transglutaminases (mTgs) are functionally similar to the human homologs, they may be involved in the human disease provocation. We suggest here a potential involvement of Tgs in the pathologies such as autoimmune diseases. In this hypothesis, the endogenous mTgs that are secreted by the gut microbiota, especially in a dysbiotic configuration, are potential drivers of systemic autoimmunity, via the enzymatic posttranslational modification of peptides in the gut lumen. These mTg activities directed toward cross-linking of naïve proteins can potentially generate neo-epitopes that are not only immunogenic but may also activate some immune response cascades leading to the pathological autoimmune processes.

Highlights

Transglutaminases (EC 2.3.2.13) (Tg), i.e., protein-glutamine γ-glutamyltransferases, belong to the class of transferases
Both deamidation and transamidation reactions are the hallmark of post-translational modification of proteins (PTMP) performed by Tgs
Microbial transglutaminases are used extensively as additives in food processing industry and the production; the biocatalytic properties and other industrial aspects of microbial transglutaminase (mTg) are covered well in a number of recent reviews (Yokoyama et al, 2004; Kieliszek and Misiewicz, 2014; Strop, 2014; Lerner and Matthias, 2015a,c,e). mTgs are considered, at least by producers, to be safe, non-toxic, non-allergenic, not immunogenic, and not pathogenic, The main aim of this review is to evaluate the potential effects that could be exerted by the mTgs in the human gastrointestinal tract following their ingestion with the industrially processed food

Summary

Introduction

Transglutaminases (EC 2.3.2.13) (Tg), i.e., protein-glutamine γ-glutamyltransferases, belong to the class of transferases. They catalyze the formation of an isopeptide bond between the acyl group at the end of the side chain of protein- or peptide-bound glutamine residues and the first order ε-amine groups of protein- or peptide-bound lysine. Deamination occurs if there is an absence of free amine groups In this case, water acts as an acyl acceptor. Both deamidation and transamidation reactions are the hallmark of post-translational modification of proteins (PTMP) performed by Tgs. Tgs include nine enzyme families and they form a superfamily the representatives of which can be found in all Archaea and in some Bacteria

Objectives

Conclusion