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Comprehensive Detection of Isopeptides between Human Tissue Transglutaminase and Gluten Peptides

Lexhaller, Barbara; Ludwig, Christina; Scherf, Katharina Anne

Abstract:
Celiac disease (CD) is a chronic inflammation of the small intestine triggered by the ingestion of gluten in genetically predisposed individuals. Tissue transglutaminase (TG2) is a key factor in CD pathogenesis, because it catalyzes both the deamidation of specific glutamine residues and the formation of covalent N ε-( γ-glutamyl)-lysine isopeptide crosslinks resulting in TG2–gluten peptide complexes. These complexes are thought to activate B cells causing the secretion of anti-TG2 autoantibodies that serve as diagnostic markers for CD, although their pathogenic role remains unclear. To gain more insight into the molecular structures of TG2-gluten peptide complexes, we used different proteomics software tools that enable the comprehensive identification of isopeptides. Thus, 34 different isopeptides involving 20 TG2 lysine residues were identified in a model system, only six of which were previously known. Additionally, 36 isopeptides of TG2-TG2 multimers were detected. Experiments with different TG2-gluten peptide molar ratios revealed the most preferred lysine residues involved in isopeptide crosslinking. Expanding the model system to three gluten peptides with more glutamine residues allowed the localization of the preferred glutamine crosslinking sites. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000098686
Veröffentlicht am 04.10.2019
Coverbild
Zugehörige Institution(en) am KIT Institut für Angewandte Biowissenschaften (IAB)
Publikationstyp Zeitschriftenaufsatz
Jahr 2019
Sprache Englisch
Identifikator ISSN: 2072-6643
KITopen-ID: 1000098686
Erschienen in Nutrients
Band 11
Heft 10
Seiten Art. Nr.: 2263
Vorab online veröffentlicht am 20.09.2019
Schlagworte celiac disease, crosslink, deamidation, gliadin, gluten, isopeptides, LC-MS/MS, tissue transglutaminase, transamidation
Nachgewiesen in Scopus
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