Towards the understanding of the early stages of gliadin intolerance disorders using a supramolecular perspective

MARÍA HERRERA; LUCIANO BENEDINI; TANIA VEUTHEY; CAROLINE LONEZ; THOMAS HELLWEG; JEAN-MARIE RUYSSCHAERT; VERÓNICA DODERO

Buenos Aires

Congreso; Ubiquitin & ubiquitin-like proteins: At the crossroads from chromatin to protein; 2014

Embo-conicet

Gliadin, a protein present in wheat, rye and barley undergoes incomplete enzymatic degradation during digestion, producing several peptides. One of them is a 33-mer peptide,LQLQPF(PQPQLPY)3PQPQPF, a proline-rich fragment which is associated with gluten sensitivity and celiac disease (CD) [1]. The initial pathogenic mechanism is still unknown, however, it is clear that the immune system is involved. In this regard, CD is associated with the presence of one copy of the HLA-DQ2 heterodimer and less frequently in 6% of the patients with the HLA-DQ8 molecule. The up regulation of Ubiquitin D (UBD) is associated with intestinal mucosa of active CD [2]. Recently, our group demonstrated that the 33-mer gliadin peptide is able to self- assembleinto spherical and linear oligomers under physiological conditions. A conformational transition from PPII to beta-sheet was observed during the self-assembly process [3]. Our recent results show a connection between 33-mer supramolecular assemblies and inflammation, which can be relevant inthe early steps of gliadin intolerance disorders. A supramolecular perspective is presented.