Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase

Detalhes bibliográficos
Autor(a) principal: da Silva, Marco Túlio Alves
Data de Publicação: 2020
Outros Autores: E Silva, Ivan Rosa, Faim, Lívia Maria, Bellini, Natália Karla, Pereira, Murilo Leão, Lima, Ana Laura, de Jesus, Teresa Cristina Leandro, Costa, Fernanda Cristina, Watanabe, Tatiana Faria [UNESP], Pereira, Humberto D’Muniz, Valentini, Sandro Roberto [UNESP], Zanelli, Cleslei Fernando [UNESP], Borges, Júlio Cesar, Dias, Marcio Vinicius Bertacine, da Cunha, Júlia Pinheiro Chagas, Mittra, Bidyottam, Andrews, Norma W., Thiemann, Otavio Henrique
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1371/journal.pntd.0008091
http://hdl.handle.net/11449/208104
Resumo: Eukaryotes from the Excavata superphylum have been used as models to study the evolution of cellular molecular processes. Strikingly, human parasites of the Trypanosomatidae family (T. brucei, T. cruzi and L. major) conserve the complex machinery responsible for selenocysteine biosynthesis and incorporation in selenoproteins (SELENOK/SelK, SELE-NOT/SelT and SELENOTryp/SelTryp), although these proteins do not seem to be essential for parasite viability under laboratory controlled conditions. Selenophosphate synthetase (SEPHS/SPS) plays an indispensable role in selenium metabolism, being responsible for catalyzing the formation of selenophosphate, the biological selenium donor for selenocys-teine synthesis. We solved the crystal structure of the L. major selenophosphate synthetase and confirmed that its dimeric organization is functionally important throughout the domains of life. We also demonstrated its interaction with selenocysteine lyase (SCLY) and showed that it is not present in other stable assemblies involved in the selenocysteine pathway, namely the phosphoseryl-tRNASec kinase (PSTK)-Sec-tRNASec synthase (SEPSECS) complex and the tRNASec-specific elongation factor (eEFSec) complex. Endoplasmic reticulum stress with dithiothreitol (DTT) or tunicamycin upon selenophosphate synthetase ablation in procyclic T. brucei cells led to a growth defect. On the other hand, only DTT presented a negative effect in bloodstream T. brucei expressing selenophosphate synthetase-RNAi. Furthermore, selenoprotein T (SELENOT) was dispensable for both forms of the parasite. Together, our data suggest a role for the T. brucei selenophosphate synthetase in the regulation of the parasite’s ER stress response.
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spelling Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyaseEukaryotes from the Excavata superphylum have been used as models to study the evolution of cellular molecular processes. Strikingly, human parasites of the Trypanosomatidae family (T. brucei, T. cruzi and L. major) conserve the complex machinery responsible for selenocysteine biosynthesis and incorporation in selenoproteins (SELENOK/SelK, SELE-NOT/SelT and SELENOTryp/SelTryp), although these proteins do not seem to be essential for parasite viability under laboratory controlled conditions. Selenophosphate synthetase (SEPHS/SPS) plays an indispensable role in selenium metabolism, being responsible for catalyzing the formation of selenophosphate, the biological selenium donor for selenocys-teine synthesis. We solved the crystal structure of the L. major selenophosphate synthetase and confirmed that its dimeric organization is functionally important throughout the domains of life. We also demonstrated its interaction with selenocysteine lyase (SCLY) and showed that it is not present in other stable assemblies involved in the selenocysteine pathway, namely the phosphoseryl-tRNASec kinase (PSTK)-Sec-tRNASec synthase (SEPSECS) complex and the tRNASec-specific elongation factor (eEFSec) complex. Endoplasmic reticulum stress with dithiothreitol (DTT) or tunicamycin upon selenophosphate synthetase ablation in procyclic T. brucei cells led to a growth defect. On the other hand, only DTT presented a negative effect in bloodstream T. brucei expressing selenophosphate synthetase-RNAi. Furthermore, selenoprotein T (SELENOT) was dispensable for both forms of the parasite. Together, our data suggest a role for the T. brucei selenophosphate synthetase in the regulation of the parasite’s ER stress response.Laboratory of Structural Biology Sao Carlos Institute of Physics University of São PauloLaboratory of Cell Cycle and Center of Toxins Immune Response and Cell Signaling-CeTICS Butantan InstituteLondon School of Hygiene and Tropical MedicineSchool of Pharmaceutical Sciences São Paulo State University (UNESP)São Carlos Institute of Chemistry University of São PauloDepartment of Microbiology Institute of Biomedical Science University of São PauloDepartment of Cell Biology and Molecular Genetics University of MarylandDepartment of Genetics and Evolution Federal University of São CarlosSchool of Pharmaceutical Sciences São Paulo State University (UNESP)Universidade de São Paulo (USP)Butantan InstituteLondon School of Hygiene and Tropical MedicineUniversidade Estadual Paulista (Unesp)University of MarylandUniversidade Federal de São Carlos (UFSCar)da Silva, Marco Túlio AlvesE Silva, Ivan RosaFaim, Lívia MariaBellini, Natália KarlaPereira, Murilo LeãoLima, Ana Laurade Jesus, Teresa Cristina LeandroCosta, Fernanda CristinaWatanabe, Tatiana Faria [UNESP]Pereira, Humberto D’MunizValentini, Sandro Roberto [UNESP]Zanelli, Cleslei Fernando [UNESP]Borges, Júlio CesarDias, Marcio Vinicius Bertacineda Cunha, Júlia Pinheiro ChagasMittra, BidyottamAndrews, Norma W.Thiemann, Otavio Henrique2021-06-25T11:06:22Z2021-06-25T11:06:22Z2020-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1-31http://dx.doi.org/10.1371/journal.pntd.0008091PLoS Neglected Tropical Diseases, v. 14, n. 10, p. 1-31, 2020.1935-27351935-2727http://hdl.handle.net/11449/20810410.1371/journal.pntd.00080912-s2.0-8509497329815256654089001950000-0001-7831-1149Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPLoS Neglected Tropical Diseasesinfo:eu-repo/semantics/openAccess2024-06-24T13:07:52Zoai:repositorio.unesp.br:11449/208104Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:38:41.290904Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase
title Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase
spellingShingle Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase
da Silva, Marco Túlio Alves
title_short Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase
title_full Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase
title_fullStr Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase
title_full_unstemmed Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase
title_sort Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase
author da Silva, Marco Túlio Alves
author_facet da Silva, Marco Túlio Alves
E Silva, Ivan Rosa
Faim, Lívia Maria
Bellini, Natália Karla
Pereira, Murilo Leão
Lima, Ana Laura
de Jesus, Teresa Cristina Leandro
Costa, Fernanda Cristina
Watanabe, Tatiana Faria [UNESP]
Pereira, Humberto D’Muniz
Valentini, Sandro Roberto [UNESP]
Zanelli, Cleslei Fernando [UNESP]
Borges, Júlio Cesar
Dias, Marcio Vinicius Bertacine
da Cunha, Júlia Pinheiro Chagas
Mittra, Bidyottam
Andrews, Norma W.
Thiemann, Otavio Henrique
author_role author
author2 E Silva, Ivan Rosa
Faim, Lívia Maria
Bellini, Natália Karla
Pereira, Murilo Leão
Lima, Ana Laura
de Jesus, Teresa Cristina Leandro
Costa, Fernanda Cristina
Watanabe, Tatiana Faria [UNESP]
Pereira, Humberto D’Muniz
Valentini, Sandro Roberto [UNESP]
Zanelli, Cleslei Fernando [UNESP]
Borges, Júlio Cesar
Dias, Marcio Vinicius Bertacine
da Cunha, Júlia Pinheiro Chagas
Mittra, Bidyottam
Andrews, Norma W.
Thiemann, Otavio Henrique
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Butantan Institute
London School of Hygiene and Tropical Medicine
Universidade Estadual Paulista (Unesp)
University of Maryland
Universidade Federal de São Carlos (UFSCar)
dc.contributor.author.fl_str_mv da Silva, Marco Túlio Alves
E Silva, Ivan Rosa
Faim, Lívia Maria
Bellini, Natália Karla
Pereira, Murilo Leão
Lima, Ana Laura
de Jesus, Teresa Cristina Leandro
Costa, Fernanda Cristina
Watanabe, Tatiana Faria [UNESP]
Pereira, Humberto D’Muniz
Valentini, Sandro Roberto [UNESP]
Zanelli, Cleslei Fernando [UNESP]
Borges, Júlio Cesar
Dias, Marcio Vinicius Bertacine
da Cunha, Júlia Pinheiro Chagas
Mittra, Bidyottam
Andrews, Norma W.
Thiemann, Otavio Henrique
description Eukaryotes from the Excavata superphylum have been used as models to study the evolution of cellular molecular processes. Strikingly, human parasites of the Trypanosomatidae family (T. brucei, T. cruzi and L. major) conserve the complex machinery responsible for selenocysteine biosynthesis and incorporation in selenoproteins (SELENOK/SelK, SELE-NOT/SelT and SELENOTryp/SelTryp), although these proteins do not seem to be essential for parasite viability under laboratory controlled conditions. Selenophosphate synthetase (SEPHS/SPS) plays an indispensable role in selenium metabolism, being responsible for catalyzing the formation of selenophosphate, the biological selenium donor for selenocys-teine synthesis. We solved the crystal structure of the L. major selenophosphate synthetase and confirmed that its dimeric organization is functionally important throughout the domains of life. We also demonstrated its interaction with selenocysteine lyase (SCLY) and showed that it is not present in other stable assemblies involved in the selenocysteine pathway, namely the phosphoseryl-tRNASec kinase (PSTK)-Sec-tRNASec synthase (SEPSECS) complex and the tRNASec-specific elongation factor (eEFSec) complex. Endoplasmic reticulum stress with dithiothreitol (DTT) or tunicamycin upon selenophosphate synthetase ablation in procyclic T. brucei cells led to a growth defect. On the other hand, only DTT presented a negative effect in bloodstream T. brucei expressing selenophosphate synthetase-RNAi. Furthermore, selenoprotein T (SELENOT) was dispensable for both forms of the parasite. Together, our data suggest a role for the T. brucei selenophosphate synthetase in the regulation of the parasite’s ER stress response.
publishDate 2020
dc.date.none.fl_str_mv 2020-10-01
2021-06-25T11:06:22Z
2021-06-25T11:06:22Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1371/journal.pntd.0008091
PLoS Neglected Tropical Diseases, v. 14, n. 10, p. 1-31, 2020.
1935-2735
1935-2727
http://hdl.handle.net/11449/208104
10.1371/journal.pntd.0008091
2-s2.0-85094973298
1525665408900195
0000-0001-7831-1149
url http://dx.doi.org/10.1371/journal.pntd.0008091
http://hdl.handle.net/11449/208104
identifier_str_mv PLoS Neglected Tropical Diseases, v. 14, n. 10, p. 1-31, 2020.
1935-2735
1935-2727
10.1371/journal.pntd.0008091
2-s2.0-85094973298
1525665408900195
0000-0001-7831-1149
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PLoS Neglected Tropical Diseases
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 1-31
dc.source.none.fl_str_mv Scopus
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instname_str Universidade Estadual Paulista (UNESP)
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institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
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