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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/45430
Ver los metadatos del registro completo
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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 |
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1846082788376182784 |
score |
13.22299 |