Oligomerization and structural transition of gluten peptides. Are gluten-related disorders a new protein aggregation disease?

HERRERA, M.G; DODERO, V.I.

Berlin

Congreso; 8th Peptide Engineering Meeting; 2018

Oligomerization and structural transition of gluten peptides.Are gluten-related disorders a new protein aggregation disease?M. Georgina Herrera and Veronica I. DoderoUniversität Bielefeld, Universitätstr. 25, Bielefeld-Germanyveronica.dodero@uni-bielefeld.deGluten is a complex protein matrix present in wheat, rye, barley and some varieties of oats. Inwheat, gliadin is the protein associated with gluten-related disorders, like celiac disease butalso related to other diseases like autism (1). The gliadin protein is not fully degraded byhumans producing an immunodominant fragment of 33 amino acid (33-mer) that triggersdifferent immune responses in susceptible individuals. The cause and the early events that leadto the loss of its tolerance are not understood. However, it is accepted that intestinal tissuetransglutaminase transforms three specific glutamines (Q) of 33-mer to glutamic acids (E)obtaining the most immunoreactive peptide 33-mer (E) peptide (2).Recently, we revealed that the 33-mer oligomerizes under physiological conditions formingdifferent size oligomers and fibril-like structures (3). During the self-assembly process, astructural transition towards the characteristic amyloid β parallel structure occurs (4). Based onthe structural and morphological similarities with amyloid aggregation, we moved fromchemistry and biophysics to immunological research, reporting that only large structures of 33-mer induce an innate immune response in macrophages mediated by human Toll-like receptor4 (TLR4) (5).  Here, we will present insights into the 33-mer structural transition and oligomerization togetherwith new evidence about 33-mer (E) oligomerization behavior under physiological conditions.Our findings open a new understanding of the early stages of gluten-related disorders situatingthem, at least in vitro, as a new protein aggregation disease. References:(1) K. Servick, The war on gluten, Science 360 (2018) 848.(2) L. M. Lammers, M G. Herrera, V. I. Dodero, Translational Chemistry meets gluten-related disorders,ChemistryOpen 7 (2018) 217.(3) M. G. Herrera, F. Zamarreño, M. Costabel, H. Ritacco, A. Hütten, N. Sewald, V. I. Dodero, CircularDichroism and Electron Microscopy Studies in vitro of 33-mer Gliadin Peptide revealed SecondaryStructure Transition and Supramolecular Organization, Biopolymers 101 (2014) 96.(4) M. G. Herrera, L. A. Benedini, C. Lonez, P. L. Schilardi, T. Hellweg, J.-M. Ruysschaert, V. I. Dodero,Self-assembly of 33-mer gliadin peptide oligomers, Soft Matter 11 (2015) 8648.(5) M. G. Herrera, M. Pizzuto. C. Lonez, K. Rott, A. Hütten, N. Sewald, J-M Ruysschaert, V. I. Dodero,Large Supramolecular Structures of 33-mer Gliadin Peptide Activate Toll-like Receptors in Macrophages,Nanomedicine: NBM (2018), doi:10.1016/j.nano.2018.04.014.