A New Class of Thioredoxin‐Related Protein Able to Bind Iron-Sulfur Clusters

Authors
Bisio, Hugo; Bonilla, Mariana; Manta, Bruno; Graña, Martin; Salzman, Valentina; Aguilar, Pablo Sebastián; Gladyshev, Vadim; Comini, Marcelo; Salinas, Gustavo
Publication Year
2015
Language
English
Format
article
Status
Published version
Description
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
Subject
LEVADURAS
REDOX
TIOREDOXINA
MITOCONDRIA
Inmunología
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/49367