ArticleBiochimie2018
Zinc(II) binding on human wild-type ISCU and Met140 variants modulates NFS1 desulfurase activity.
Article in Biochimie, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 22 citations in OpenAlex.
- Approximate size and preliminary composition of the low-mass zinc pool in the cytosol of Saccharomyces cerevisiae.The Journal of biological chemistry · 2026Article
- The human zinc-binding cysteine proteome.Cell · 2025Article
- Two-stage binding of mitochondrial ferredoxin-2 to the core iron-sulfur cluster assembly complex.Nature communications · 2024Article
- Iron-sulfur protein odyssey: exploring their cluster functional versatility and challenging identification.Metallomics : integrated biometal science · 2024Review
- Structure of a putative immature form of a Rieske-type iron-sulfur protein in complex with zinc chloride.Communications chemistry · 2023Article
- Structural diversity of cysteine desulfurases involved in iron-sulfur cluster biosynthesis.Biophysics and physicobiology · 2022Article
- Molecular Mechanism of ISC Iron-Sulfur Cluster Biogenesis Revealed by High-Resolution Native Mass Spectrometry.Journal of the American Chemical Society · 2020Article
- Mammalian iron-sulfur cluster biogenesis: Recent insights into the roles of frataxin, acyl carrier protein and ATPase-mediated transfer to recipient proteins.Current opinion in chemical biology · 2020Review
- Unique roles of iron and zinc binding to the yeast Fe-S cluster scaffold assembly protein "Isu1".Metallomics : integrated biometal science · 2019Article
- Physiologically relevant reconstitution of iron-sulfur cluster biosynthesis uncovers persulfide-processing functions of ferredoxin-2 and frataxin.Nature communications · 2019Article
- Mechanism of frataxin "bypass" in human iron-sulfur cluster biosynthesis with implications for Friedreich's ataxia.The Journal of biological chemistry · 2019Article
- Structure of the human frataxin-bound iron-sulfur cluster assembly complex provides insight into its activation mechanism.Nature communications · 2019Article
- The role of chaperones in iron-sulfur cluster biogenesis.FEBS letters · 2018Review
- NMR as a Tool to Investigate the Processes of Mitochondrial and Cytosolic Iron-Sulfur Cluster Biosynthesis.Molecules (Basel, Switzerland) · 2018Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Human de novo iron-sulfur (Fe-S) assembly complex consists of cysteine desulfurase NFS1, accessory protein ISD11, acyl carrier protein ACP, scaffold protein ISCU, and allosteric activator frataxin (FXN). FXN binds the NFS1-ISD11-ACP-ISCU complex (SDAU), to activate the desulfurase activity and Fe-S cluster biosynthesis. In the absence of FXN, the NFS1-ISD11-ACP (SDA) complex was reportedly inhibited by binding of recombinant ISCU. Recent studies also reported a substitution at position Met141 on the yeast ISCU orthologue Isu, to Ile, Leu, Val, or Cys, could bypass the requirement of FXN for Fe-S cluster biosynthesis and cell viability. Here, we show that recombinant human ISCU binds zinc(II) ion, as previously demonstrated with the E. coli orthologue IscU. Surprisingly, the relative proportion between zinc-bound and zinc-depleted forms varies among purification batches. Importantly the presence of zinc in ISCU impacts SDAU desulfurase activity. Indeed, removal of zinc(II) ion from ISCU causes a moderate but significant increase in activity compared to SDA alone, and FXN can activate both zinc-depleted and zinc-bound forms of ISCU complexed to SDA. Taking into consideration the inhibition of desulfurase activity by zinc-bound ISCU, we characterized wild type ISCU and the M140I, M140L, and M140V variants under both zinc-bound and zinc-depleted conditions, and did not observe significant differences in the biochemical and biophysical properties between wild-type and variants. Importantly, in the absence of FXN, ISCU variants behaved like wild-type and did not stimulate the desulfurase activity of the SDA complex. This study therefore identifies an important regulatory role for zinc-bound ISCU in modulation of the human Fe-S assembly system in vitro and reports no 'FXN bypass' effect on mutations at position Met140 in human ISCU. Furthermore, this study also calls for caution in interpreting studies involving recombinant ISCU by taking into consideration the influence of the bound zinc(II) ion on SDAU complex activity.
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