Involvement of cell surface TG2 in the aggregation of K562 cells triggered by gluten


Gluten-induced aggregation of K562 cells represents an in vitro model reproducing the early steps occurring in the small bowel of celiac patients exposed to gliadin. Despite the clear involvement of TG2 in the activation of the antigen-presenting cells, it is not yet clear in which compartment it occurs. Herein we study the calcium-dependent aggregation of these cells, using either cell-permeable or cell-impermeable TG2 inhibitors. Gluten induces efficient aggregation when calcium is absent in the extracellular environment, while TG2 inhibitors do not restore the full aggregating potential of gluten in the presence of calcium. These findings suggest that TG2 activity is not essential in the cellular aggregation mechanism. We demonstrate that gluten contacts the cells and provokes their aggregation through a mechanism involving the A-gliadin peptide 31-43. This peptide also activates the cell surface associated extracellular TG2 in the absence of calcium. Using a bioinformatics approach, we identify the possible docking sites of this peptide on the open and closed TG2 structures. Peptide docks with the closed TG2 structure near to the GTP/GDP site, by establishing molecular interactions with the same amino acids involved in stabilization of GTP binding. We suggest that it may occur through the displacement of GTP, switching the TG2 structure from the closed to the active open conformation. Furthermore, docking analysis shows peptide binding with the β-sandwich domain of the closed TG2 structure, suggesting that this region could be responsible for the different aggregating effects of gluten shown in the presence or absence of calcium. We deduce from these data a possible mechanism of action by which gluten makes contact with the cell surface, which could have possible implications in the celiac disease onset.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research
Additional Information: The final publication is available at Springer via
Uncontrolled Keywords: agglutination,gluten,K562 cells,TG2,TG2-inhibitors,Biochemistry,Clinical Biochemistry,Organic Chemistry
Publication ISSN: 1438-2199
Last Modified: 17 Jun 2024 07:22
Date Deposited: 27 Oct 2016 13:45
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://link.spr ... 0726-016-2339-4 (Publisher URL)
PURE Output Type: Article
Published Date: 2017-03-01
Published Online Date: 2016-10-03
Accepted Date: 2016-09-26
Submitted Date: 2016-06-06
Authors: Feriotto, G.
Calza, R.
Bergamini, C.M.
Griffin, M. (ORCID Profile 0000-0003-3824-306X)
Wang, Z. (ORCID Profile 0000-0002-2212-8318)
Beninati, S.
Ferretti, V.
Marzola, E.
Guerrini, R.
Pagnoni, A.
Cavazzini, A.
Casciano, F.
Mischiati, C.



Version: Accepted Version

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