The eukaryotic P loop NTPase Nbp35: an essential component of the cytosolic and nuclear iron-sulfur protein assembly machinery.
Soluble P loop NTPases represent a large protein family and are involved in diverse cellular functions. Here, we functionally characterized the first member of the Mrp/Nbp35 subbranch of this family, the essential Nbp35p of Saccharomyces cerevisiae. The protein resides in the cytosol and nucleus and carries an Fe/S cluster at its N terminus. Assembly of the Fe/S cluster requires the mitochondrial Fe/S cluster (ISC)-assembly and -export machineries. Depletion of Nbp35p strongly impairs the activity of the cytosolic Fe/S protein, isopropylmalate isomerase (Leu1p), whereas mitochondrial Fe/S enzymes are unaffected. Moreover, defects in the de novo maturation of various cytosolic and nuclear Fe/S proteins were observed in the absence of Nbp35p, demonstrating the functional involvement of Nbp35p in the biogenesis of extramitochondrial Fe/S proteins. Furthermore, Nbp35p genetically interacts with the closely similar P loop NTPase, Cfd1p, and the hydrogenase-like Nar1p, both of which were recently shown to perform a crucial function in cytosolic and nuclear Fe/S protein biogenesis. Hence, our study suggests that eukaryotic Nbp35 NTPases function in Fe/S protein maturation. The findings provide strong evidence for the existence of a highly conserved and essential machinery dedicated to assembling cytosolic and nuclear Fe/S proteins.
Hausmann
Anja
A
Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Robert-Koch-Strasse 6, D-35033 Marburg, Germany.
Aguilar Netz
Daili J
DJ
Balk
Janneke
J
Pierik
Antonio J
AJ
Mühlenhoff
Ulrich
U
Lill
Roland
R
D000251:Adenosine Triphosphatases / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*
D007506:Iron-Sulfur Proteins; C102265:NBP35 protein, S cerevisiae; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins
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