The canonical pathway for selenocysteine insertion is dispensable in
            <i>Trypanosomes</i>

Aeby, Eric; Palioura, Sotiria; Pusnik, Mascha; Marazzi, Janine; Lieberman, Allyson; Ullu, Elisabetta; Söll, Dieter; Schneider, André

doi:10.1073/pnas.0901575106

Cited by 31 publications

(42 citation statements)

References 29 publications

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“…75 Se labeling studies carried out with wild-type and LdSepSecS null mutants helped in ascertaining a role for LdSepSecS in selenoprotein synthesis in Leishmania as no selenoproteins could be detected in the lysate of the null mutant parasites. This is consistent with earlier studies in Trypanosome where the presence of the three selenoproteins corresponding to the predicted molecular masses of the kinetoplastid homologs, SelK (9.5 kDa), SelT (28.8 kDa), and SelTryp (89 kDa) have been reported (10,12). Cassago et al (11) had earlier reported that the genes for glutathione peroxidase, selenoprotein R and selenoprotein SPS2 homologues in Leishmania have evolved into nonselenium-containing proteins.…”

Section: Discussionsupporting

confidence: 90%

“…Similar results have been previously reported in case of T. brucei, where the pathway for selenocysteine insertion was found to be dispensable (10,42).…”

Section: Discussionsupporting

confidence: 80%

“…Selenoprotein production is abolished in the E. coli ⌬selA deletion strain JS1. Complementation of the JS1 strain with archaeal SepSecS and PSTK genes from M. jannaschii (MJ0610) has been reported to restore selenoprotein biosynthesis, as detected by FDH H activity (10). Transformants grown anaerobically were layered with top agar containing formate and benzyl viologen.…”

Section: Resultsmentioning

confidence: 99%

“…After growth, the plates were removed from the anaerobic jar and immediately overlaid with 0.75% top agar (containing 1 mg/ml of benzyl viologen, 0.25 M sodium formate, and 25 mM KH 2 PO 4 , pH 7.0). The appearance of the blue/purple color is an indication of active FDH H (10).…”

Section: Expression and Purification Of Recombinant Ldsepsecsmentioning

confidence: 99%

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Leishmania donovani Encodes a Functional Selenocysteinyl-tRNA Synthase

Manhas¹,

Gowri²,

Madhubala

2016

Journal of Biological Chemistry

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The synthesis of selenocysteine, the 21st amino acid, occurs on its transfer RNA (tRNA), tRNA Sec . tRNA Sec is initially aminoacylated with serine by seryl-tRNA synthetase and the resulting seryl moiety is converted to phosphoserine by O-phosphoseryl-tRNA kinase (PSTK) in eukaryotes. The selenium donor, selenophosphate is synthesized from selenide and ATP by selenophosphate synthetase. Selenocysteinyl-tRNA synthase (SepSecS) then uses the O-phosphoseryl-tRNA Sec and selenophosphate to form Sec-tRNA Sec in eukaryotes. Here, we report the characterization of selenocysteinyl-tRNA synthase from Leishmania donovani. Kinetoplastid SepSecS enzymes are phylogenetically closer to worm SepSecS. LdSepSecS was found to exist as a tetramer. Leishmania SepSecS enzyme was found to be active and able to complement the ⌬selA deletion in Escherichia coli JS1 strain only in the presence of archaeal PSTK, indicating the conserved nature of the PSTK-SepSecS pathway. LdSepSecS was found to localize in the cytoplasm of the parasite. Gene deletion studies indicate that Leishmania SepSecS is dispensable for the parasite survival. The parasite was found to encode three selenoproteins, which were only expressed in the presence of SepSecS. Selenoproteins of L. donovani are not required for the growth of the promastigotes. Auranofin, a known inhibitor of selenoprotein synthesis showed the same sensitivity toward the wild-type and null mutants suggesting its effect is not through binding to selenoproteins. The three-dimensional structural comparison indicates that human and Leishmania homologs are structurally highly similar but their association modes leading to tetramerization seem different.

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Section: Discussionsupporting

confidence: 90%

“…Similar results have been previously reported in case of T. brucei, where the pathway for selenocysteine insertion was found to be dispensable (10,42).…”

Section: Discussionsupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Section: Expression and Purification Of Recombinant Ldsepsecsmentioning

confidence: 99%

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Leishmania donovani Encodes a Functional Selenocysteinyl-tRNA Synthase

Manhas¹,

Gowri²,

Madhubala

2016

Journal of Biological Chemistry

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“…The insertion of selenium into Sec-dependent enzymes requires the formation of a highly reactive reduced selenium donor compound monoselenophosphate. Monoselenophosphate synthesis is catalyzed by SPS in a 1:1 ratio from selenide and ATP [5,[15][16][17].…”

Section: Specific Characteristics Of Kinetoplas-tid Selenocysteine Bimentioning

confidence: 99%

Biological Implications of Selenium and its Role in Trypanosomiasis Treatment

Silva¹,

Silva²,

Thiemann³

2014

CMC

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Selenium (Se) is an essential trace element for several organisms and is present in proteins as selenocysteine (Sec or U), an amino acid that is chemically distinct from serine and cysteine by a single atom (Se instead of O or S, respectively). Sec is incorporated into selenoproteins at an in-frame UGA codon specified by an mRNA stem-loop structure called the selenocysteine incorporating sequence (SECIS) presented in selenoprotein mRNA and specific selenocysteine synthesis and incorporation machinery. Selenoproteins are presented in all domains but are not found in all organisms. Although several functions have been attributed to this class, the majority of the proteins are involved in oxidative stress defense. Here, we discuss the kinetoplastid selenocysteine pathway and how selenium supplementation is able to alter the infection course of trypanosomatids in detail. These organisms possess the canonical elements required for selenoprotein production such as phosphoseryl tRNA kinase (PSTK), selenocysteine synthase (SepSecS), selenophosphase synthase (SelD or SPS), and elongation factor EFSec (SelB), whereas other important factors presented in mammal cells, such as SECIS binding protein 2 (SBP) and SecP 43, are absent. The selenoproteome of trypanosomatids is small, as is the selenoproteome of others parasites, which is in contrast to the large number of selenoproteins found in bacteria, aquatic organisms and higher eukaryotes. Trypanosoma and Leishmania are sensitive to auranofin, a potent selenoprotein inhibitor; however, the probable drug mechanism is not related to selenoproteins in kinetoplastids. Selenium supplementation decreases the parasitemia of various Trypanosome infections and reduces important parameters associated with diseases such as anemia and parasite-induced organ damage. New experiments are necessary to determine how selenium acts, but evidence suggests that immune response modulation and increased host defense against oxidative stress contribute to control of the parasite infection.

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Selenoproteome of Kinetoplastids

Lobanov

Gladyshev

2013

Trypanosomatid Diseases

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The canonical pathway for selenocysteine insertion is dispensable in Trypanosomes

Cited by 31 publications

References 29 publications

Leishmania donovani Encodes a Functional Selenocysteinyl-tRNA Synthase

Leishmania donovani Encodes a Functional Selenocysteinyl-tRNA Synthase

Biological Implications of Selenium and its Role in Trypanosomiasis Treatment

Selenoproteome of Kinetoplastids

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