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Article

Molecular and Structural Parallels between Gluten Pathogenic Peptides and Bacterial-Derived Proteins by Bioinformatics Analysis

1
Grupo de Biología Estructural y Biotecnología (GBEyB-IMBICE), Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Sáenz Peña 352, Bernal B1876BXD, Buenos Aires, Argentina
2
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, Ciudad Autónoma C1033AAJ, Buenos Aires, Argentina
3
Department of Chemistry, Organic Chemistry OCIII, Universität Bielefeld, Universitätsstraße 25, 33615 Bielefeld, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: Genetics and Genomics of Plants, Center for Biotechnology (CeBiTec) and Faculty of Biology, Universität Bielefeld, Universitätsstraße 25, 33615 Bielefeld, Germany.
Academic Editors: Francesco Asnicar and Serena Manara
Int. J. Mol. Sci. 2021, 22(17), 9278; https://doi.org/10.3390/ijms22179278
Received: 12 August 2021 / Revised: 23 August 2021 / Accepted: 25 August 2021 / Published: 27 August 2021
(This article belongs to the Special Issue Human Gut Microbiome and Diet in Health and Disease)
Gluten-related disorders (GRDs) are a group of diseases that involve the activation of the immune system triggered by the ingestion of gluten, with a worldwide prevalence of 5%. Among them, Celiac disease (CeD) is a T-cell-mediated autoimmune disease causing a plethora of symptoms from diarrhea and malabsorption to lymphoma. Even though GRDs have been intensively studied, the environmental triggers promoting the diverse reactions to gluten proteins in susceptible individuals remain elusive. It has been proposed that pathogens could act as disease-causing environmental triggers of CeD by molecular mimicry mechanisms. Additionally, it could also be possible that unrecognized molecular, structural, and physical parallels between gluten and pathogens have a relevant role. Herein, we report sequence, structural and physical similarities of the two most relevant gluten peptides, the 33-mer and p31-43 gliadin peptides, with bacterial pathogens using bioinformatics going beyond the molecular mimicry hypothesis. First, a stringent BLASTp search using the two gliadin peptides identified high sequence similarity regions within pathogen-derived proteins, e.g., extracellular proteins from Streptococcus pneumoniae and Granulicatella sp. Second, molecular dynamics calculations of an updated α-2-gliadin model revealed close spatial localization and solvent-exposure of the 33-mer and p31-43 peptide, which was compared with the pathogen-related proteins by homology models and localization predictors. We found putative functions of the identified pathogen-derived sequence by identifying T-cell epitopes and SH3/WW-binding domains. Finally, shape and size parallels between the pathogens and the superstructures of gliadin peptides gave rise to novel hypotheses about activation of innate immunity and dysbiosis. Based on our structural findings and the similarities with the bacterial pathogens, evidence emerges that these pathologically relevant gluten-derived peptides could behave as non-replicating pathogens opening new research questions in the interface of innate immunity, microbiome, and food research. View Full-Text
Keywords: celiac disease; non-celiac gluten sensitivity; SH3 and WW domains; 33-mer peptide; p31-43 peptide; gliadin epitopes; pathogens; sequence similarity; innate immune response celiac disease; non-celiac gluten sensitivity; SH3 and WW domains; 33-mer peptide; p31-43 peptide; gliadin epitopes; pathogens; sequence similarity; innate immune response
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MDPI and ACS Style

Vazquez, D.S.; Schilbert, H.M.; Dodero, V.I. Molecular and Structural Parallels between Gluten Pathogenic Peptides and Bacterial-Derived Proteins by Bioinformatics Analysis. Int. J. Mol. Sci. 2021, 22, 9278. https://doi.org/10.3390/ijms22179278

AMA Style

Vazquez DS, Schilbert HM, Dodero VI. Molecular and Structural Parallels between Gluten Pathogenic Peptides and Bacterial-Derived Proteins by Bioinformatics Analysis. International Journal of Molecular Sciences. 2021; 22(17):9278. https://doi.org/10.3390/ijms22179278

Chicago/Turabian Style

Vazquez, Diego S., Hanna M. Schilbert, and Veronica I. Dodero. 2021. "Molecular and Structural Parallels between Gluten Pathogenic Peptides and Bacterial-Derived Proteins by Bioinformatics Analysis" International Journal of Molecular Sciences 22, no. 17: 9278. https://doi.org/10.3390/ijms22179278

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