A New Class of Thioredoxin‐Related Protein Able to Bind Iron–Sulfur Clusters
| العنوان: | A New Class of Thioredoxin‐Related Protein Able to Bind Iron–Sulfur Clusters |
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| المؤلفون: | S AguilarPablo, SalinasGustavo, BonillaMariana, A CominiMarcelo, GrañaMartín, BisioHugo, N GladyshevVadim, SalzmanValentina, MantaBruno |
| المصدر: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| بيانات النشر: | Mary Ann Liebert Inc, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, CIENCIAS MÉDICAS Y DE LA SALUD, Protein family, Physiology, Clinical Biochemistry, chemistry.chemical_element, Reductase, Biology, Biochemistry, Redox, 03 medical and health sciences, Tioredoxina, Glutaredoxin, Mitocondria, Molecular Biology, General Environmental Science, 030102 biochemistry & molecular biology, purl.org/becyt/ford/3.1 [https], Cell Biology, Bioquímica y Biología Molecular, Yeast strain, Sulfur, Complementation, Original Research Communications, Medicina Básica, chemistry, General Earth and Planetary Sciences, purl.org/becyt/ford/3 [https], Thioredoxin, Levaduras |
| الوصف: | AIMS:Members of the thioredoxin (Trx) protein family participate mainly in redox pathways and have not been associated with Fe/S binding, in contrast to some closely related glutaredoxins (Grxs). Cestode parasites possess an unusual diversity of Trxs and Trx-related proteins with non-explored functions. Here we addressed the biochemical characterization of a new class of Trx-related protein (IsTRP) and a classical monothiol Grx (EgGrx5) from the human pathogen Echinococcus granulosus.RESULTS:The dimeric form of IsTRP coordinates Fe2S2 in a glutathione-independent manner; instead, Fe/S binding relies on the CXXC motif conserved among Trxs. This novel binding mechanism allows holo-IsTRP to be highly resistant to oxidation. IsTRP lacks canonical reductase activities. Mitochondrially targeted IsTRP aids growth of a Grx5 null yeast strain. Similar complementation assays performed with EgGrx5 revealed functional conservation for class II Grxs despite the presence of non-conserved structural elements. IsTRP is a cestode-lineage specific protein highly expressed in the gravid adult worm, which releases the infective stage critical for dissemination.INNOVATION:IsTRP is the first member from the thioredoxin family to be reported to bind Fe/S. We disclose a novel mechanism of Fe/S coordination within the Trx folding unit, which renders the cluster highly resistant to oxidation-mediated disassembly.CONCLUSION:We demonstrate that IsTRP defines a new protein family within the thioredoxin superfamily, confirm the conservation of function for class II glutaredoxin from non-phylogenetically related species and highlight the versatility of the Trx folding unit to acquire Fe/S binding as a recurrent emergent function. Fil: Bisio, Hugo. Instituto Pasteur de Montevideo; Uruguay Fil: Bonilla, Mariana. Instituto Pasteur de Montevideo; Uruguay Fil: Manta, Bruno. Instituto Pasteur de Montevideo; Uruguay Fil: Graña, Martin. Instituto Pasteur de Montevideo; Uruguay Fil: Salzman, Valentina. Instituto Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Aguilar, Pablo Sebastián. Instituto Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gladyshev, Vadim. Harvard Medical School; Estados Unidos Fil: Comini, Marcelo. Instituto Pasteur de Montevideo; Uruguay Fil: Salinas, Gustavo. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay |
| وصف الملف: | application/pdf |
| تدمد: | 1557-7716 1523-0864 |
| DOI: | 10.1089/ars.2015.6377 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::046c159d3069d8e9b67b848a1a25f0ac https://doi.org/10.1089/ars.2015.6377 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....046c159d3069d8e9b67b848a1a25f0ac |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15577716 15230864 |
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| DOI: | 10.1089/ars.2015.6377 |