title: Circular dichroism and electron microscopy studies in vitro of 33-mer gliadin peptide revealed secondary structure transition and supramolecular organization.
abstract: Gliadin, a protein present in wheat, rye, and barley, undergoes incomplete enzymatic degradation during digestion, producing an immunogenic 33-mer peptide, LQLQPF(PQPQLPY)3 PQPQPF. The special features of 33-mer that provoke a break in its tolerance leading to gliadin sensitivity and celiac disease remains elusive. Herein, it is reported that 33-mer gliadin peptide was not only able to fold into polyproline II secondary structure but also depending on concentration resulted in conformational transition and self-assembly under aqueous condition, pH 7.0. A 33-mer dimer is presented as one initial possible step in the self-assembling process obtained by partial electrostatics charge distribution calculation and molecular dynamics. In addition, electron microscopy experiments revealed supramolecular organization of 33-mer into colloidal nanospheres. In the presence of 1 mM sodium citrate, 1 mM sodium borate, 1 mM sodium phosphate buffer, 15 mM NaCl, the nanospheres were stabilized, whereas in water, a linear organization and formation of fibrils were observed. It is hypothesized that the self-assembling process could be the result of the combination of hydrophobic effect, intramolecular hydrogen bonding, and electrostatic complementarity due to 33-mer's high content of proline and glutamine amino acids and its calculated nonionic amphiphilic character. Although, performed in vitro, these experiments have revealed new features of the 33-mer gliadin peptide that could represent an important and unprecedented event in the early stage of 33-mer interaction with the gut mucosa prior to onset of inflammation. Moreover, these findings may open new perspectives for the understanding and treatment of gliadin intolerance disorders.
authors.affiliation: Department of Chemistry, INQUISUR, National University of South, CONICET, Av. Alem 1253, 8000 Bahía Blanca, Argentina.
authors.forename: María G
authors.initials: MG
authors.lastname: Herrera
authors.forename: Fernando
authors.initials: F
authors.lastname: Zamarreño
authors.forename: Marcelo
authors.initials: M
authors.lastname: Costabel
authors.forename: Hernan
authors.initials: H
authors.lastname: Ritacco
authors.forename: Andreas
authors.initials: A
authors.lastname: Hütten
authors.forename: Norbert
authors.initials: N
authors.lastname: Sewald
authors.forename: Verónica I
authors.initials: VI
authors.lastname: Dodero
mesh_terms: D002942:Circular Dichroism; D005903:Gliadin; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry
chemical_list: D010446:Peptide Fragments; D010455:Peptides; D005903:Gliadin
keywords: 33-mer gliadin peptide; circular dichroism; electron microscopy; gliadin intolerance; supramolecular organization