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标题：Comprehensive Detection of Isopeptides between Human Tissue Transglutaminase and Gluten Peptides
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作者：Barbara Lexhaller ; Christina Ludwig ; Katharina A. Scherf 等
期刊名称：Nutrients
电子版ISSN：2072-6643
出版年度：2019
卷号：11
期号：10
页码：2263-2287
DOI：10.3390/nu11102263
出版社：MDPI Publishing
摘要：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 Nε-(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. These new insights into the structure of TG2-gluten peptide complexes may help clarify the role of extracellular TG2 in CD autoimmunity and in other inflammatory diseases.
关键词：celiac disease; crosslink; deamidation; gliadin; gluten; isopeptides; LC-MS/MS; tissue transglutaminase; transamidation celiac disease ; crosslink ; deamidation ; gliadin ; gluten ; isopeptides ; LC-MS/MS ; tissue transglutaminase ; transamidation