Beta structure motif recognition by anti-gliadin antibodies in coeliac disease.
A 20-amino acid synthetic peptide from the N-terminal region of gamma3 avenin yields a surprisingly strong reactivity with anti-gliadin antibodies (AGA) of coeliac sera, comparable to that of a gliadin extract. In contrast, a low reactivity is observed with five similar peptides derived from alpha-gliadin, gamma70 and omega1 secalins. Circular dichroism studies of these peptides show that the avenin peptide displays the highest beta-turn content (30%), while other peptides yield much lower values. In agreement with circular dichroism data, nuclear magnetic resonance data point to the presence of a beta-turn in the avenin peptide DPSEQ segment, a sequence with a high statistical beta-turn preference. A strong linear dependence between AGA reactivity and beta-turn content was observed for these peptides, indicating for the first time a role of beta-turn motifs in anti-gliadin antibodies recognition in coeliac disease. This suggests that circulating AGA in coeliac patients comprise not only linear but also conformational antibodies against beta-turn motifs. Polyclonal antibodies raised against the avenin peptide containing beta-turn motifs react by immunoblotting with all gliadin, hordein and secalin proteins, which are rich in beta-turn conformations, despite that their primary structures are unrelated to that of the peptide.
Alfonso
P
P
Structural Analysis of Proteins Unit, Centro Nacional de Biotecnologia, CSIC, Cantoblanco, Madrid, Spain.
Soto
C
C
Albar
J P
JP
Camafeita
E
E
Escobar
H
H
Suárez
L
L
Rico
M
M
Bruix
M
M
Méndez
E
E
D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D002446:Celiac Disease / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005903:Gliadin / Q000737:chemistry / Q000276:immunology*; D005983:Glutens; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology; D055315:Prolamins; D017433:Protein Structure, Secondary
D000906:Antibodies; D010455:Peptides; D010940:Plant Proteins; D055315:Prolamins; D005983:Glutens; D005903:Gliadin