Molecular mechanisms of 33-mer gliadin peptide oligomerisation

The proteolytic resistant 33-mer gliadin peptide is an immunodominant fragment in gluten and responsible for the celiac disease and other gluten-related disorders. Meanwhile, the primary structure of the 33-mer is associated with the adaptive immune response in celiac patients, and the structural tr...

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Detalles Bibliográficos
Autores: Amundarain, María Julia, Herrera, Maria Georgina, Zamarreño, Fernando, Viso, Juan Francisco, Costabel, Marcelo Daniel, Dodero, Veronica Isabel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/115222
Acceso en línea:http://hdl.handle.net/11336/115222
Access Level:acceso abierto
Palabra clave:33-mer
GLIADIN
MOLECULAR DYNAMICS
OLIGOMERISATION
https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
id AR_33e02a8fea0f0f0f04877fbc2035c8e1
oai_identifier_str oai:ri.conicet.gov.ar:11336/115222
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Molecular mechanisms of 33-mer gliadin peptide oligomerisation
title Molecular mechanisms of 33-mer gliadin peptide oligomerisation
spellingShingle Molecular mechanisms of 33-mer gliadin peptide oligomerisation
Amundarain, María Julia
33-mer
GLIADIN
MOLECULAR DYNAMICS
OLIGOMERISATION
https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
title_short Molecular mechanisms of 33-mer gliadin peptide oligomerisation
title_full Molecular mechanisms of 33-mer gliadin peptide oligomerisation
title_fullStr Molecular mechanisms of 33-mer gliadin peptide oligomerisation
title_full_unstemmed Molecular mechanisms of 33-mer gliadin peptide oligomerisation
title_sort Molecular mechanisms of 33-mer gliadin peptide oligomerisation
dc.creator.none.fl_str_mv Amundarain, María Julia
Herrera, Maria Georgina
Zamarreño, Fernando
Viso, Juan Francisco
Costabel, Marcelo Daniel
Dodero, Veronica Isabel
author Amundarain, María Julia
author_facet Amundarain, María Julia
Herrera, Maria Georgina
Zamarreño, Fernando
Viso, Juan Francisco
Costabel, Marcelo Daniel
Dodero, Veronica Isabel
author_role author
author2 Herrera, Maria Georgina
Zamarreño, Fernando
Viso, Juan Francisco
Costabel, Marcelo Daniel
Dodero, Veronica Isabel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv 33-mer
GLIADIN
MOLECULAR DYNAMICS
OLIGOMERISATION
https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
topic 33-mer
GLIADIN
MOLECULAR DYNAMICS
OLIGOMERISATION
https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
description The proteolytic resistant 33-mer gliadin peptide is an immunodominant fragment in gluten and responsible for the celiac disease and other gluten-related disorders. Meanwhile, the primary structure of the 33-mer is associated with the adaptive immune response in celiac patients, and the structural transformation of the 33-mer into protofilaments activates a primordial innate immune response in human macrophages. This means that accumulation, oligomerisation and structural transformation of the 33-mer could be the unknown first event that triggers the disease. Herein, we reveal the early stepwise mechanism of 33-mer oligomerisation by combining multiple computational simulations, tyrosine cross-linking, fluorescence spectroscopy and circular dichroism experiments. Our theoretical findings demonstrated that the partial charge distribution along the 33-mer molecule and the presence of glutamine that favours H-bonds between the oligomers are the driving forces that trigger oligomerisation. The high content of proline is critical for the formation of the flexible PPII secondary structure that led to a β structure transition upon oligomerisation. Experimentally, we stabilised the 33-mer small oligomers by dityrosine cross-linking, detecting from dimers to higher molecular weight oligomers, which confirmed our simulations. The relevance of 33-mer oligomers as a trigger of the disease as well as its inhibition may be a novel therapeutic strategy for the treatment of gluten-related disorders.
publishDate 2019
dc.date.none.fl_str_mv 2019-09-23
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/115222
Amundarain, María Julia; Herrera, Maria Georgina; Zamarreño, Fernando; Viso, Juan Francisco; Costabel, Marcelo Daniel; et al.; Molecular mechanisms of 33-mer gliadin peptide oligomerisation; Royal Society of Chemistry; Physical Chemistry Chemical Physics; 21; 40; 23-9-2019; 22539-22552
1463-9076
CONICET Digital
CONICET
url http://hdl.handle.net/11336/115222
identifier_str_mv Amundarain, María Julia; Herrera, Maria Georgina; Zamarreño, Fernando; Viso, Juan Francisco; Costabel, Marcelo Daniel; et al.; Molecular mechanisms of 33-mer gliadin peptide oligomerisation; Royal Society of Chemistry; Physical Chemistry Chemical Physics; 21; 40; 23-9-2019; 22539-22552
1463-9076
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1039/C9CP02338K
info:eu-repo/semantics/altIdentifier/url/https://pubs.rsc.org/en/journals/journalissues/cp#!issueid=cp021040&type=current&issnprint=1463-9076
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1799195610963771392
spelling Molecular mechanisms of 33-mer gliadin peptide oligomerisationAmundarain, María JuliaHerrera, Maria GeorginaZamarreño, FernandoViso, Juan FranciscoCostabel, Marcelo DanielDodero, Veronica Isabel33-merGLIADINMOLECULAR DYNAMICSOLIGOMERISATIONhttps://purl.org/becyt/ford/1.3https://purl.org/becyt/ford/1The proteolytic resistant 33-mer gliadin peptide is an immunodominant fragment in gluten and responsible for the celiac disease and other gluten-related disorders. Meanwhile, the primary structure of the 33-mer is associated with the adaptive immune response in celiac patients, and the structural transformation of the 33-mer into protofilaments activates a primordial innate immune response in human macrophages. This means that accumulation, oligomerisation and structural transformation of the 33-mer could be the unknown first event that triggers the disease. Herein, we reveal the early stepwise mechanism of 33-mer oligomerisation by combining multiple computational simulations, tyrosine cross-linking, fluorescence spectroscopy and circular dichroism experiments. Our theoretical findings demonstrated that the partial charge distribution along the 33-mer molecule and the presence of glutamine that favours H-bonds between the oligomers are the driving forces that trigger oligomerisation. The high content of proline is critical for the formation of the flexible PPII secondary structure that led to a β structure transition upon oligomerisation. Experimentally, we stabilised the 33-mer small oligomers by dityrosine cross-linking, detecting from dimers to higher molecular weight oligomers, which confirmed our simulations. The relevance of 33-mer oligomers as a trigger of the disease as well as its inhibition may be a novel therapeutic strategy for the treatment of gluten-related disorders.Fil: Amundarain, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Herrera, Maria Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universitat Bielefeld; AlemaniaFil: Zamarreño, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Viso, Juan Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Costabel, Marcelo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Dodero, Veronica Isabel. Universitat Bielefeld; AlemaniaRoyal Society of Chemistry2019-09-23info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/115222Amundarain, María Julia; Herrera, Maria Georgina; Zamarreño, Fernando; Viso, Juan Francisco; Costabel, Marcelo Daniel; et al.; Molecular mechanisms of 33-mer gliadin peptide oligomerisation; Royal Society of Chemistry; Physical Chemistry Chemical Physics; 21; 40; 23-9-2019; 22539-225521463-9076CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1039/C9CP02338Kinfo:eu-repo/semantics/altIdentifier/url/https://pubs.rsc.org/en/journals/journalissues/cp#!issueid=cp021040&type=current&issnprint=1463-9076info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:57:57Zoai:ri.conicet.gov.ar:11336/115222instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:57:57.804CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
score 15,811543

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