Tah18 transfers electrons to Dre2 in cytosolic iron-sulfur protein biogenesis.
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.
Netz
Daili J A
DJ
Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Marburg, Germany.
Stümpfig
Martin
M
Doré
Carole
C
Mühlenhoff
Ulrich
U
Pierik
Antonio J
AJ
Lill
Roland
R
D003600:Cytosol / Q000737:chemistry / Q000378:metabolism*; D004579:Electron Transport; D004583:Electrons; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013466:Sulfurtransferases / Q000378:metabolism; D013997:Time Factors
C489114:CIAPIN1 protein, human; C531900:Dre2 protein, S cerevisiae; D005420:Flavoproteins; D047908:Intracellular Signaling Peptides and Proteins; D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D009249:NADP; C478386:NDOR1 protein, human; D010088:Oxidoreductases; C552878:Tah18 protein, S cerevisiae; D013466:Sulfurtransferases; C115912:NFS1 protein, S cerevisiae
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