Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei

Autores
Guerrero, Sergio Adrian; Arias, Diego Gustavo; Cabeza, Matías Sebastián; Law, Michelle C. Y.; D'Amico, Maria; Kumar, Ambika; Wilkinson, Shane R.
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
To combat the deleterious effects that oxidation of the sulfur atom in methionine to sulfoxide may bring, aerobic cells express repair pathways involving methionine sulfoxide reductases (MSRs) to reverse the above reaction. Here, we show that Trypanosoma brucei, the causative agent of African trypanosomiasis, expresses two distinct trypanothione-dependent MSRs that can be distinguished from each other based on sequence, sub-cellular localisation and substrate preference. One enzyme found in the parasite´s cytosol, shows homology to the MSRA family of repair proteins and preferentially metabolises the S epimer of methionine sulfoxide. The second, which contains sequence motifs present in MSRBs, is restricted to the mitochondrion and can only catalyse reduction of the R form of peptide-bound methionine sulfoxide. The importance of these proteins to the parasite was demonstrated using functional genomic-based approaches to produce cells with reduced or elevated expression levels of MSRA, which exhibited altered susceptibility to exogenous H2O2. These findings identify new reparative pathways that function to fix oxidatively damaged methionine within this medically important parasite.
Fil: Guerrero, Sergio Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina
Fil: Arias, Diego Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina
Fil: Cabeza, Matías Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina
Fil: Law, Michelle C. Y.. Queen Mary University of London; Reino Unido
Fil: D'Amico, Maria. Queen Mary University of London; Reino Unido
Fil: Kumar, Ambika. Queen Mary University of London; Reino Unido
Fil: Wilkinson, Shane R.. Queen Mary University of London; Reino Unido
Materia
Gfp
Methionine
Recombinant Protein Expression
Rna Interference
Trypanosoma Brucei
Trypanothione
Tryparedoxin
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/45430
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/45430
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma bruceiGuerrero, Sergio AdrianArias, Diego GustavoCabeza, Matías SebastiánLaw, Michelle C. Y.D'Amico, MariaKumar, AmbikaWilkinson, Shane R.GfpMethionineRecombinant Protein ExpressionRna InterferenceTrypanosoma BruceiTrypanothioneTryparedoxinhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1To combat the deleterious effects that oxidation of the sulfur atom in methionine to sulfoxide may bring, aerobic cells express repair pathways involving methionine sulfoxide reductases (MSRs) to reverse the above reaction. Here, we show that Trypanosoma brucei, the causative agent of African trypanosomiasis, expresses two distinct trypanothione-dependent MSRs that can be distinguished from each other based on sequence, sub-cellular localisation and substrate preference. One enzyme found in the parasite´s cytosol, shows homology to the MSRA family of repair proteins and preferentially metabolises the S epimer of methionine sulfoxide. The second, which contains sequence motifs present in MSRBs, is restricted to the mitochondrion and can only catalyse reduction of the R form of peptide-bound methionine sulfoxide. The importance of these proteins to the parasite was demonstrated using functional genomic-based approaches to produce cells with reduced or elevated expression levels of MSRA, which exhibited altered susceptibility to exogenous H2O2. These findings identify new reparative pathways that function to fix oxidatively damaged methionine within this medically important parasite.Fil: Guerrero, Sergio Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Arias, Diego Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Cabeza, Matías Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Law, Michelle C. Y.. Queen Mary University of London; Reino UnidoFil: D'Amico, Maria. Queen Mary University of London; Reino UnidoFil: Kumar, Ambika. Queen Mary University of London; Reino UnidoFil: Wilkinson, Shane R.. Queen Mary University of London; Reino UnidoElsevier Science Inc2017-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/45430Guerrero, Sergio Adrian; Arias, Diego Gustavo; Cabeza, Matías Sebastián; Law, Michelle C. Y.; D'Amico, Maria; et al.; Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei; Elsevier Science Inc; Free Radical Biology and Medicine; 112; 11-2017; 524-5330891-5849CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0891584917307396info:eu-repo/semantics/altIdentifier/doi/10.1016/j.freeradbiomed.2017.08.023info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:30:52Zoai:ri.conicet.gov.ar:11336/45430instacron: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:34982025-10-15 14:30:53.26CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei
title Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei
spellingShingle Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei
Guerrero, Sergio Adrian
Gfp
Methionine
Recombinant Protein Expression
Rna Interference
Trypanosoma Brucei
Trypanothione
Tryparedoxin
title_short Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei
title_full Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei
title_fullStr Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei
title_full_unstemmed Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei
title_sort Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei
dc.creator.none.fl_str_mv Guerrero, Sergio Adrian
Arias, Diego Gustavo
Cabeza, Matías Sebastián
Law, Michelle C. Y.
D'Amico, Maria
Kumar, Ambika
Wilkinson, Shane R.
author Guerrero, Sergio Adrian
author_facet Guerrero, Sergio Adrian
Arias, Diego Gustavo
Cabeza, Matías Sebastián
Law, Michelle C. Y.
D'Amico, Maria
Kumar, Ambika
Wilkinson, Shane R.
author_role author
author2 Arias, Diego Gustavo
Cabeza, Matías Sebastián
Law, Michelle C. Y.
D'Amico, Maria
Kumar, Ambika
Wilkinson, Shane R.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Gfp
Methionine
Recombinant Protein Expression
Rna Interference
Trypanosoma Brucei
Trypanothione
Tryparedoxin
topic Gfp
Methionine
Recombinant Protein Expression
Rna Interference
Trypanosoma Brucei
Trypanothione
Tryparedoxin
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv To combat the deleterious effects that oxidation of the sulfur atom in methionine to sulfoxide may bring, aerobic cells express repair pathways involving methionine sulfoxide reductases (MSRs) to reverse the above reaction. Here, we show that Trypanosoma brucei, the causative agent of African trypanosomiasis, expresses two distinct trypanothione-dependent MSRs that can be distinguished from each other based on sequence, sub-cellular localisation and substrate preference. One enzyme found in the parasite´s cytosol, shows homology to the MSRA family of repair proteins and preferentially metabolises the S epimer of methionine sulfoxide. The second, which contains sequence motifs present in MSRBs, is restricted to the mitochondrion and can only catalyse reduction of the R form of peptide-bound methionine sulfoxide. The importance of these proteins to the parasite was demonstrated using functional genomic-based approaches to produce cells with reduced or elevated expression levels of MSRA, which exhibited altered susceptibility to exogenous H2O2. These findings identify new reparative pathways that function to fix oxidatively damaged methionine within this medically important parasite.
Fil: Guerrero, Sergio Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina
Fil: Arias, Diego Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina
Fil: Cabeza, Matías Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina
Fil: Law, Michelle C. Y.. Queen Mary University of London; Reino Unido
Fil: D'Amico, Maria. Queen Mary University of London; Reino Unido
Fil: Kumar, Ambika. Queen Mary University of London; Reino Unido
Fil: Wilkinson, Shane R.. Queen Mary University of London; Reino Unido
description To combat the deleterious effects that oxidation of the sulfur atom in methionine to sulfoxide may bring, aerobic cells express repair pathways involving methionine sulfoxide reductases (MSRs) to reverse the above reaction. Here, we show that Trypanosoma brucei, the causative agent of African trypanosomiasis, expresses two distinct trypanothione-dependent MSRs that can be distinguished from each other based on sequence, sub-cellular localisation and substrate preference. One enzyme found in the parasite´s cytosol, shows homology to the MSRA family of repair proteins and preferentially metabolises the S epimer of methionine sulfoxide. The second, which contains sequence motifs present in MSRBs, is restricted to the mitochondrion and can only catalyse reduction of the R form of peptide-bound methionine sulfoxide. The importance of these proteins to the parasite was demonstrated using functional genomic-based approaches to produce cells with reduced or elevated expression levels of MSRA, which exhibited altered susceptibility to exogenous H2O2. These findings identify new reparative pathways that function to fix oxidatively damaged methionine within this medically important parasite.
publishDate 2017
dc.date.none.fl_str_mv 2017-11
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/11336/45430
Guerrero, Sergio Adrian; Arias, Diego Gustavo; Cabeza, Matías Sebastián; Law, Michelle C. Y.; D'Amico, Maria; et al.; Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei; Elsevier Science Inc; Free Radical Biology and Medicine; 112; 11-2017; 524-533
0891-5849
CONICET Digital
CONICET
url http://hdl.handle.net/11336/45430
identifier_str_mv Guerrero, Sergio Adrian; Arias, Diego Gustavo; Cabeza, Matías Sebastián; Law, Michelle C. Y.; D'Amico, Maria; et al.; Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei; Elsevier Science Inc; Free Radical Biology and Medicine; 112; 11-2017; 524-533
0891-5849
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0891584917307396
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.freeradbiomed.2017.08.023
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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_ 1846082788376182784
score 13.22299

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