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 unexplored functions. In this study, 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 nonconserved 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 Trx 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 Trx superfamily, confirm the conservation of function for class II Grx from nonphylogenetically related species, and highlight the versatility of the Trx folding unit to acquire Fe/S binding as a recurrent emergent function. Antioxid. Redox Signal. 00, 000-000.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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