Molecular mechanisms of 33-mer gliadin peptide oligomerisation

Julia Amundarain M, Herrera M, Zamarreno F, Francisco Viso J, Costabel MD, Dodero VI (2019)
PHYSICAL CHEMISTRY CHEMICAL PHYSICS 21(40): 22539-22552.

Zeitschriftenaufsatz | Veröffentlicht| Englisch
 
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Autor/in
Julia Amundarain, Maria; Herrera, Maria ; Zamarreno, Fernando; Francisco Viso, Juan; Costabel, Marcelo D.; Dodero, Veronica IsabelUniBi
Abstract / Bemerkung
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 beta 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.
Erscheinungsjahr
2019
Zeitschriftentitel
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
Band
21
Ausgabe
40
Seite(n)
22539-22552
ISSN
1463-9076
eISSN
1463-9084
Page URI
https://pub.uni-bielefeld.de/record/2938744

Zitieren

Julia Amundarain M, Herrera M, Zamarreno F, Francisco Viso J, Costabel MD, Dodero VI. Molecular mechanisms of 33-mer gliadin peptide oligomerisation. PHYSICAL CHEMISTRY CHEMICAL PHYSICS. 2019;21(40):22539-22552.
Julia Amundarain, M., Herrera, M., Zamarreno, F., Francisco Viso, J., Costabel, M. D., & Dodero, V. I. (2019). Molecular mechanisms of 33-mer gliadin peptide oligomerisation. PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 21(40), 22539-22552. doi:10.1039/c9cp02338k
Julia Amundarain, M., Herrera, M., Zamarreno, F., Francisco Viso, J., Costabel, M. D., and Dodero, V. I. (2019). Molecular mechanisms of 33-mer gliadin peptide oligomerisation. PHYSICAL CHEMISTRY CHEMICAL PHYSICS 21, 22539-22552.
Julia Amundarain, M., et al., 2019. Molecular mechanisms of 33-mer gliadin peptide oligomerisation. PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 21(40), p 22539-22552.
M. Julia Amundarain, et al., “Molecular mechanisms of 33-mer gliadin peptide oligomerisation”, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, vol. 21, 2019, pp. 22539-22552.
Julia Amundarain, M., Herrera, M., Zamarreno, F., Francisco Viso, J., Costabel, M.D., Dodero, V.I.: Molecular mechanisms of 33-mer gliadin peptide oligomerisation. PHYSICAL CHEMISTRY CHEMICAL PHYSICS. 21, 22539-22552 (2019).
Julia Amundarain, Maria, Herrera, Maria, Zamarreno, Fernando, Francisco Viso, Juan, Costabel, Marcelo D., and Dodero, Veronica Isabel. “Molecular mechanisms of 33-mer gliadin peptide oligomerisation”. PHYSICAL CHEMISTRY CHEMICAL PHYSICS 21.40 (2019): 22539-22552.

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