Open AccessTrypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase
Author(s) -
Marco Túlio Alves da Silva,
Ivan Rosa e Silva,
Lívia Maria Faim,
Natália Karla Bellini,
Murilo Leão Pereira,
Ana Laura Lima,
Teresa Cristina Leandro de Jesus,
Fernanda Cristina Costa,
Tatiana F. Watanabe,
H.M. Pereira,
Sandro Roberto Valentini,
Cleslei Fernando Zanelli,
Júlio César Borges,
Márcio Vinícius Bertacini Dias,
Júlia Pinheiro Chagas da Cunha,
Bidyottam Mittra,
Norma W. Andrews,
Otávio Henrique Thiemann
Publication year - 2020
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0008091
Subject(s) - selenocysteine , chemistry , function (biology) , biochemistry , lyase , cysteine , biology , genetics , enzyme
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, 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 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-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 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.