Abstract
Cytosolic and nuclear iron-sulfur (Fe-S) proteins play key roles in processes such as ribosome maturation, transcription and DNA repair-replication. For biosynthesis of their Fe-S clusters, a dedicated cytosolic Fe-S protein assembly (CIA) machinery is required. Here, we identify the essential flavoprotein Tah18 as a previously unrecognized CIA component and show by cell biological, biochemical and spectroscopic approaches that the complex of Tah18 and the CIA protein Dre2 is part of an electron transfer chain functioning in an early step of cytosolic Fe-S protein biogenesis. Electrons are transferred from NADPH via the FAD- and FMN-containing Tah18 to the Fe-S clusters of Dre2. This electron transfer chain is required for assembly of target but not scaffold Fe-S proteins, suggesting a need for reduction in the generation of stably inserted Fe-S clusters. The pathway is conserved in eukaryotes, as human Ndor1–Ciapin1 proteins can functionally replace yeast Tah18–Dre2.
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Acknowledgements
We thank S. Molik for plasmid construction and D. Vogel for help with cloning. We acknowledge generous support from the Deutsche Forschungsgemeinschaft (SFB 593, the Gottfried-Wilhelm Leibniz program and GRK 1216), Rhön Klinikum AG, von Behring-Röntgen Stiftung, LOEWE program of state Hessen, Max-Planck Gesellschaft and Fonds der chemischen Industrie.
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D.J.A.N., U.M., A.J.P. and R.L. designed experiments and analyzed data. All authors performed experiments. D.J.A.N., A.J.P. and R.L. wrote the manuscript.
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Netz, D., Stümpfig, M., Doré, C. et al. Tah18 transfers electrons to Dre2 in cytosolic iron-sulfur protein biogenesis. Nat Chem Biol 6, 758–765 (2010). https://doi.org/10.1038/nchembio.432
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DOI: https://doi.org/10.1038/nchembio.432
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