Jump to main content
Jump to site search

Issue 40, 2019
Previous Article Next Article

Molecular mechanisms of 33-mer gliadin peptide oligomerisation

Author affiliations


The proteolytic resistant 33-mer gliadin peptide is an immunodominant fragment in gluten and responsible for the celiac disease and other gluten-related disorders. Meanwhile, the primary structure of the 33-mer is associated with the adaptive immune response in celiac patients, and the structural transformation of the 33-mer into protofilaments activates a primordial innate immune response in human macrophages. This means that accumulation, oligomerisation and structural transformation of the 33-mer could be the unknown first event that triggers the disease. Herein, we reveal the early stepwise mechanism of 33-mer oligomerisation by combining multiple computational simulations, tyrosine cross-linking, fluorescence spectroscopy and circular dichroism experiments. Our theoretical findings demonstrated that the partial charge distribution along the 33-mer molecule and the presence of glutamine that favours H-bonds between the oligomers are the driving forces that trigger oligomerisation. The high content of proline is critical for the formation of the flexible PPII secondary structure that led to a β structure transition upon oligomerisation. Experimentally, we stabilised the 33-mer small oligomers by dityrosine cross-linking, detecting from dimers to higher molecular weight oligomers, which confirmed our simulations. The relevance of 33-mer oligomers as a trigger of the disease as well as its inhibition may be a novel therapeutic strategy for the treatment of gluten-related disorders.

Graphical abstract: Molecular mechanisms of 33-mer gliadin peptide oligomerisation

Back to tab navigation

Supplementary files

Publication details

The article was received on 25 Apr 2019, accepted on 23 Sep 2019 and first published on 23 Sep 2019

Article type: Paper
DOI: 10.1039/C9CP02338K
Phys. Chem. Chem. Phys., 2019,21, 22539-22552

  •   Request permissions

    Molecular mechanisms of 33-mer gliadin peptide oligomerisation

    M. J. Amundarain, M. G. Herrera, F. Zamarreño, J. F. Viso, M. D. Costabel and V. I. Dodero, Phys. Chem. Chem. Phys., 2019, 21, 22539
    DOI: 10.1039/C9CP02338K

Search articles by author