title: Kinetic and functional characterisation of the heparin-binding peptides from human transglutaminase 2.
abstract: Transglutaminase 2 (TG2) is an autoantigen in celiac disease (CD) and it has multiple biologic functions including involvement in cell adhesion through interactions with integrins, fibronectin (FN), and heparan sulfate proteoglycans. We aimed to delineate the heparin-binding regions of human TG2 by studying binding kinetics of the predicted heparin-binding peptides using surface plasmon resonance method. In addition, we characterized immunogenicity of the TG2 peptides and their effect on cell adhesion. The high-affinity binding of human TG2 to the immobilized heparin was observed, and two TG2 peptides, P1 (amino acids 202-215) and P2 (261-274), were found to bind heparin. The amino acid sequences corresponding to the heparin-binding peptides were located close to each other on the surface of the TG2 molecule as part of the α-helical structures. The heparin-binding peptides displayed increased immunoreactivity against serum IgA of CD patients compared with other TG2 peptides. The cell adhesion reducing effect of the peptide P2 was revealed in Caco-2 intestinal epithelial cell attachment to the FN and FN-TG2 coated surfaces. We propose that TG2 amino acid sequences 202-215 and 261-274 could be involved in binding of TG2 to cell surface heparan sulfates. High immunoreactivity of the corresponding heparin-binding peptides of TG2 with CD patient's IgA supports the previously described role of anti-TG2 autoantibodies interfering with this interaction.
authors.affiliation: Immunology Group, Department of General and Molecular Pathology, University of Tartu, Ravila 19, 50411, Tartu, Estonia. kaupo.teesalu@ut.ee
authors.forename: Kaupo
authors.initials: K
authors.lastname: Teesalu
authors.forename: Oivi
authors.initials: O
authors.lastname: Uibo
authors.forename: Raivo
authors.initials: R
authors.lastname: Uibo
authors.forename: Meeme
authors.initials: M
authors.lastname: Utt
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D001798:Blood Proteins / Q000737:chemistry* / Q000494:pharmacology; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019204:GTP-Binding Proteins / Q000737:chemistry*; D006801:Humans; D007223:Infant; D007700:Kinetics; D008297:Male; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D020349:Surface Plasmon Resonance; D011503:Transglutaminases / Q000737:chemistry*
chemical_list: C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D010455:Peptides; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins