| Full text | |
| Author(s): Show less - |
Alves da Silva, Marco Tulio
[1]
;
Rosa e Silva, Ivan
[1]
;
Faim, Livia Maria
[1]
;
Bellini, Natalia Karla
[1]
;
Pereira, Murilo Leao
[1]
;
Lima, Ana Laura
[1]
;
Leandro de Jesus, Teresa Cristina
[1, 2]
;
Costa, Fernanda Cristina
[3, 1]
;
Watanabe, Tatiana Faria
[4]
;
Pereira, Humberto D'Muniz
[1]
;
Valentini, Sandro Roberto
[4]
;
Zanelli, Cleslei Fernando
[4]
;
Borges, Julio Cesar
[5]
;
Bertacini Dias, Marcio Vinicius
[6]
;
Chagas Cunha, Julia Pinheiro
[2]
;
Mittra, Bidyottam
[7]
;
Andrews, Norma W.
[7]
;
Thiemann, Otavio Henrique
[8, 1]
Total Authors: 18
|
| Affiliation: | [1] Univ Sao Paulo, Sao Carlos Inst Phys, Lab Struct Biol, Sao Carlos, SP - Brazil
[2] Butantan Inst, Special Lab Appl Toxinol, Sao Paulo, SP - Brazil
[3] London Sch Hyg & Trop Med, London - England
[4] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Araraquara, SP - Brazil
[5] Univ Sao Paulo, Sao Carlos Inst Chem, Sao Carlos, SP - Brazil
[6] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo, SP - Brazil
[7] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 - USA
[8] Univ Fed Sao Carlos, Dept Genet & Evolut, Sao Carlos, SP - Brazil
Total Affiliations: 8
|
| Document type: | Journal article |
| Source: | PLoS Neglected Tropical Diseases; v. 14, n. 10 OCT 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
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.cruziandL.major) conserve the complex machinery responsible for selenocysteine biosynthesis and incorporation in selenoproteins (SELENOK/SelK, SELENOT/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 selenocysteine synthesis. We solved the crystal structure of theL.majorselenophosphate 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-tRNA(Sec)kinase (PSTK)-Sec-tRNA(Sec)synthase (SEPSECS) complex and the tRNA(Sec)-specific elongation factor (eEFSec) complex. Endoplasmic reticulum stress with dithiothreitol (DTT) or tunicamycin upon selenophosphate synthetase ablation in procyclicT.bruceicells led to a growth defect. On the other hand, only DTT presented a negative effect in bloodstreamT.bruceiexpressing selenophosphate synthetase-RNAi. Furthermore, selenoprotein T (SELENOT) was dispensable for both forms of the parasite. Together, our data suggest a role for theT.bruceiselenophosphate synthetase in the regulation of the parasite's ER stress response. Author summary Selenium is both a toxic compound and a micronutrient. As a micronutrient, it participates in the synthesis of specific proteins, selenoproteins, as the amino acid selenocysteine. The synthesis of selenocysteine is present in organisms ranging from bacteria to humans. The protist parasites of the Trypanosomatidae family, that cause major tropical diseases, conserve the complex machinery responsible for selenocysteine biosynthesis and incorporation in selenoproteins. However, this pathway has been considered dispensable for the parasitic protist cells. This has intrigued us, and lead to question that if maintained in the cell it should be under selective pressure and therefore be necessary. Also, extensive and dynamic protein-protein interactions must happen to deliver selenium-containing intermediates along the pathway in order to warrant efficient usage of biological selenium in the cell. In this study we have investigated the molecular interactions of different proteins involved in selenocysteine synthesis and its putative involvement in the endoplasmic reticulum redox homeostasis. (AU) | |
| FAPESP's process: | 08/57910-0 - National Institute of Structural Biotechnology and Medicinal Chemistry in Infectious Diseases |
| Grantee: | Richard Charles Garratt |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 11/24017-4 - Study of selenium metabolism in primitive eukaryotes |
| Grantee: | Marco Túlio Alves da Silva |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 10/04429-3 - Structural Studies of Escherichia coli Selenophosphate Synthetase |
| Grantee: | Ivan Rosa e Silva |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 13/02848-7 - Selenium metabolism in primitive eukaryotes |
| Grantee: | Marco Túlio Alves da Silva |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| FAPESP's process: | 11/06087-5 - Identification and characterization of replication origins in Trypanosoma and Leishmania |
| Grantee: | Teresa Cristina Leandro de Jesus |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 07/06591-0 - Molecular characterization of the selenocisteine synthesis pathway: structural and functional investigation of the human SECp43 |
| Grantee: | Lívia Maria Faim |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |