Affinage

ISCU

Iron-sulfur cluster assembly enzyme ISCU · UniProt Q9H1K1

Length
167 aa
Mass
18.0 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ISCU is the central, universally conserved scaffold on which mitochondrial and cytosolic iron-sulfur (Fe-S) clusters are assembled de novo and from which they are delivered to apo-acceptor proteins (PMID:10891064, PMID:16517407). Cluster building proceeds sequentially on the ISCU dimer: the cysteine desulfurase NFS1/IscS binds ISCU with high affinity and transfers sulfur from its persulfide to ISCU cysteines (PMID:11577100), iron is inserted at a tetrahedral assembly site coordinated by conserved Cys, Asp, and His residues (Cys35, Asp37, Cys61, His103) (PMID:36121382, PMID:15522305), and two transient [2Fe-2S] clusters are reductively coupled — a step requiring His106 — into a single [4Fe-4S] cluster per dimer (PMID:10891064, PMID:17506525, PMID:33938220). Frataxin (FXN) acts within the NFS1-ISD11-ISCU complex as a sulfur-transfer enhancer and as the proximal Fe2+ donor, binding the desulfurase complex more tightly in the presence of ISCU and releasing its iron upon reductant addition (PMID:25597503, PMID:29576242), with ferredoxin (FDX2)/NADPH/FNR supplying the electrons for assembly and reductive coupling (PMID:25688831, PMID:17506525). ISCU is a metamorphic protein that interconverts between a largely structured (S) and a largely disordered (D) state through concerted cis-trans isomerization of conserved prolyl bonds; NFS1 and the Hsp70 chaperone (HscA/mtHSP70) bind the D-state while the J-protein co-chaperone (HscB/HSC20) binds the S-state, and this S↔D cycling is obligatory in vivo for both assembly and chaperone-driven cluster release (PMID:22203963, PMID:22782893, PMID:23110687, PMID:33202070). Completed clusters are delivered ATP-dependently through the HscA/HscB chaperone cycle to acceptors including ferredoxin and the monothiol glutaredoxin Grx5, with cluster-type and conformer specificity dictating fate: [4Fe-4S]-ISCU activates apo-aconitase and transfers chaperone-independently to NFU1, whereas [2Fe-2S]-ISCU does not (PMID:16964969, PMID:22963613, PMID:17506526, PMID:32151725). Loss of ISCU function inactivates aconitases and respiratory chain complexes, inappropriately activates iron regulatory proteins (IRP1/IRP2), and disrupts iron homeostasis (PMID:16517407). Intronic ISCU splice mutations that strengthen a cryptic splice acceptor cause tissue-specific ISCU deficiency in skeletal muscle, defining hereditary myopathy with lactic acidosis (PMID:18304497, PMID:18296749, PMID:21165651).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 High

    Establishing that IscU is a scaffold that builds Fe-S clusters in a defined sequence answered how nascent clusters are assembled before delivery to apo-enzymes.

    Evidence anaerobic chromatography with Mössbauer, resonance Raman and UV-vis spectroscopy of reconstituted IscU

    PMID:10891064

    Open questions at the time
    • Did not define the iron source in vivo
    • Coordination ligands of each cluster intermediate not yet resolved structurally
  2. 2001 High

    Demonstrating direct persulfide-based sulfur transfer from IscS to IscU cysteines defined the chemical mechanism of sulfur donation.

    Evidence [35S]-cysteine radiotracer, SPR, ITC and IscS deletion mutagenesis

    PMID:11577100

    Open questions at the time
    • Which specific IscU cysteine receives the persulfide not pinpointed here
    • Role of conformational state in binding not addressed
  3. 2000 High

    Identifying IscU as a substrate that stimulates the Hsc66/Hsc20 chaperone ATPase established that a dedicated Hsp70/J-protein system services Fe-S scaffold function.

    Evidence ATPase assays, SPR, ITC and chaperone aggregation-suppression assays

    PMID:10869428 PMID:11053447

    Open questions at the time
    • The functional output of the ATPase cycle (cluster transfer) not yet shown
    • Binding determinants on IscU undefined
  4. 2002 High

    Mapping the LPPVK (residues 99–103) motif as the Hsc66 recognition site and showing Hsc20 binds elsewhere defined how the two chaperones engage distinct IscU regions.

    Evidence phage display, peptide arrays and ATPase stimulation assays, later confirmed by a 1.95 Å HscA-peptide crystal structure

    PMID:11994302 PMID:15351650

    Open questions at the time
    • Peptide binding mode may differ from full-length IscU engagement
    • How Hsc20 recognizes the structured conformer not addressed at this stage
  5. 2004 High

    Solving the IscU fold with a metal at the assembly site and showing apo-IscU unfolds on metal removal revealed the intrinsic conformational lability central to its function.

    Evidence NMR solution structure with zinc, plus zinc chelation experiments; IscA shown separately to act as an iron donor under iron-limiting conditions

    PMID:15247288 PMID:15522305

    Open questions at the time
    • Physiological identity of the iron donor remained contested
    • Functional meaning of the order-disorder transition not yet defined
  6. 2006 High

    Showing that cluster transfer from IscU to apo-ferredoxin requires HscB and ATP hydrolysis established that the chaperone cycle drives cluster handoff, not just substrate binding.

    Evidence CD/EPR transfer kinetics and phosphate assays; parallel work showed cytosolic human ISCU/ISCS assemble clusters on IRP1, and ISCU RNAi inactivates aconitases and dysregulates iron

    PMID:16517407 PMID:16527810 PMID:16964969

    Open questions at the time
    • Mechanism coupling ATP hydrolysis to cluster release not yet structural
    • Cytosolic vs mitochondrial division of labor unresolved
  7. 2007 High

    Demonstrating reductive coupling of two [2Fe-2S] into one [4Fe-4S] and cluster-type-specific delivery to aconitase explained how ISCU produces and routes different cluster types.

    Evidence Mössbauer/resonance Raman/EPR with dithionite or Isc-ferredoxin reductant, and aconitase activation assays with the D39A discriminating mutant

    PMID:17506525 PMID:17506526

    Open questions at the time
    • Physiological reductant for coupling not definitively assigned
    • Structural basis for [4Fe-4S]-specific recognition by acceptors unknown
  8. 2008 High

    Crystallizing holo-IscU with a buried [2Fe-2S] cluster and defining the ATP-hydrolysis requirement of HscA-accelerated transfer provided the structural and energetic basis of cluster handoff.

    Evidence MAD-phased crystal structure of [2Fe-2S]-IscU and CD/ATPase analysis with the ATPase-dead HscA T212V mutant

    PMID:18723024 PMID:18986169

    Open questions at the time
    • Asymmetric oligomeric state may be crystallization-dependent
    • How cluster distortion drives release into acceptors not fully resolved
  9. 2008 High

    Identifying intronic ISCU splice mutations that deplete mitochondrial ISCU in skeletal muscle linked Fe-S scaffold deficiency to hereditary myopathy with lactic acidosis.

    Evidence genetic mapping, splice and protein analysis, IRP1 activity and iron measurements in patient muscle

    PMID:18296749 PMID:18304497

    Open questions at the time
    • Why the phenotype is muscle-restricted not yet explained at this stage
    • Therapeutic correction of splicing not addressed
  10. 2009 High

    Defining apo-IscU as a metamorphic protein interconverting between disordered (D) and structured (S) states, with HscB binding the S-state, reframed IscU function around conformational dynamics.

    Evidence NMR chemical shift perturbation, zinc stabilization, and D39A mutant analysis

    PMID:19492851

    Open questions at the time
    • Functional partner preference of the D-state not yet tested
    • Atomic basis of the conformational switch unknown
  11. 2012 High

    Assigning the D-state to NFS1/IscS binding and assembly, the S-state to HscB, and the D-state to HscA defined a conformation-coupled chaperone cycle, with prolyl isomerization as the molecular switch.

    Evidence NMR with conformationally biased variants, H/D exchange, prolyl-bond NOE analysis, and structures of S-state apo-IscU; transfer to Grx5 also shown to be HscA/HscB/ATP-dependent

    PMID:22203963 PMID:22734684 PMID:22782893 PMID:22963613 PMID:23110687

    Open questions at the time
    • Whether a prolyl isomerase catalyzes the switch in vivo not established
    • One NMR study (idx 31) reported IscU stays folded within the IscS complex, conflicting with D-state preference
  12. 2013 High

    Extending the D/S conformer-chaperone model to the human NFS1-ISD11-ISCU-mtHSP70-HSC20 system, and showing mTORC1 phosphorylates and stabilizes ISCU, connected conserved mechanism to mammalian regulation.

    Evidence NMR with human ISCU variants, ATPase and assembly assays; co-IP and in vitro kinase assay for mTORC1-ISCU(S14)

    PMID:23508953 PMID:23940031

    Open questions at the time
    • Functional consequence of S14 phosphorylation beyond stability not defined (Medium-confidence for the kinase link)
    • ISD11 role clarified only as not binding ISCU directly
  13. 2015 High

    Defining frataxin as a sulfur-transfer enhancer that accumulates persulfide on ISCU C104, and later as the proximal Fe2+ donor, resolved frataxin's biochemical role in cluster assembly.

    Evidence maleimide-peptide persulfide probing with MS; ITC/NMR iron-binding and release experiments; FDX2/NADPH/FNR shown sufficient as physiological reductant

    PMID:21298097 PMID:25597503 PMID:25688831 PMID:29576242

    Open questions at the time
    • Whether iron and sulfur are delivered in a fixed order not settled
    • Quantitative flux through frataxin vs alternative iron sources in vivo unknown
  14. 2018 High

    Showing that fully S-state-locked ISCU variants (M108I, D39V) cannot form a productive FXN/FDX2 complex with physiological reductant explained why conformational dynamics are mechanistically essential.

    Evidence NMR titrations and assembly assays comparing DTT vs reduced FDX2; FDX2 displaces FXN on locked variants

    PMID:29406711

    Open questions at the time
    • In vivo phenotypes of these specific variants not characterized here
    • Structural arrangement of the FXN/FDX2-containing complex unresolved
  15. 2020 High

    Establishing direct, conformer- and cluster-type-specific transfer from [4Fe-4S]-ISCU to NFU1, and proving in vivo that D↔S interconversion is required for function, completed the link between conformational cycling and cluster delivery.

    Evidence NMR/SAXS/ITC and cluster-transfer assays for NFU1; in vivo genetic bypass and CD spectroscopy of conformationally locked IscU variants

    PMID:32151725 PMID:33202070

    Open questions at the time
    • Determinants selecting chaperone-independent vs chaperone-dependent transfer routes unresolved
    • Full acceptor specificity hierarchy not mapped
  16. 2022 High

    Atomic-resolution definition of the dimeric assembly site, His106's role in reductive coupling, and the tetrahedral 2-Cys iron-binding mode finalized the structural model of iron insertion and cluster conversion.

    Evidence archaeal IscU crystal structure with EPR/mutagenesis; multi-spectroscopic (XAS, Mössbauer, NMR, CD, EPR) characterization of the iron-loaded site ruling out an auxiliary non-Cys site

    PMID:33938220 PMID:36121382

    Open questions at the time
    • Dynamics of iron delivery into the assembly site in real time not captured
    • How the eukaryotic complex coordinates these steps spatially not fully resolved
  17. 2014 High

    Mechanistically connecting a patient G50E mutation to impaired NFS1/HSCB interaction and downstream respiratory and ROS defects linked ISCU biochemistry to disease pathophysiology.

    Evidence interaction and assembly assays, ETC activity and ROS measurements in human cells and yeast; tissue-specific splicing and oxidative-stress destabilization explaining muscle restriction studied separately

    PMID:21165651 PMID:22125086 PMID:23035118 PMID:24573684

    Open questions at the time
    • Why splicing factors (PTBP1, IGF2BP1, RBM39) regulation is muscle-specific not fully explained (Medium-confidence)
    • Therapeutic splice correction not demonstrated in patients
  18. 2023 Medium

    Reports that copper directly inhibits ISCU and that ISCU sequesters p53 in macrophages to drive M2 polarization extend ISCU into metal-toxicity and immune-regulatory contexts beyond canonical assembly.

    Evidence in vitro copper-binding and cellular Fe-S enzyme assays in Wilson's disease models; co-IP, fractionation and macrophage polarization assays for ISCU-p53

    PMID:37225108 PMID:40541964

    Open questions at the time
    • Both are single-lab findings awaiting independent confirmation
    • Whether the p53-sequestration role is separable from Fe-S scaffold function not established
    • Physiological copper concentrations achieving inhibition not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How conformational interconversion, iron and sulfur delivery, and chaperone-driven release are coordinated in time and space within the intact eukaryotic assembly complex, and how the conflicting reports of ISCU's folded vs disordered state during desulfurase engagement are reconciled, remain open.
  • No integrated structure of the full assembly/transfer cycle
  • Conflicting NMR observations on IscU conformation in the IscS complex (idx 31 vs idx 16) unresolved
  • In vivo regulation of ISCU phosphorylation and conformational switching poorly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0140313 molecular sequestering activity 2
Localization
GO:0005739 mitochondrion 3 GO:0005829 cytosol 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1430728 Metabolism 2
Partners
FDX2FXNHSCBHSPA9ISCA1ISD11NFS1NFU1
Complex memberships
HscA/HscB-IscU chaperone complexISCU-NFS1-ISD11-frataxin quaternary complexNFS1-ISD11-ISCU cysteine desulfurase complex

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 IscU serves as a scaffold for sequential assembly of [2Fe-2S] and [4Fe-4S] clusters: IscS-mediated assembly on IscU proceeds first to one [2Fe-2S]2+ cluster per dimer, then two [2Fe-2S]2+ clusters per dimer, and finally one [4Fe-4S]2+ cluster per dimer. Both cluster types are reductively labile. [2Fe-2S] clusters show incomplete cysteinyl ligation and [4Fe-4S] cluster has non-cysteinyl ligation at a unique Fe site. Anaerobic anion exchange chromatography, UV-visible absorption, resonance Raman, and Mössbauer spectroscopies Biochemistry High 10891064
2001 IscS transfers sulfur directly to IscU via persulfide intermediates on IscU cysteine residues. IscU binds IscS with high affinity (Kd ~2 µM), sulfur transfer is inhibited by iodoacetamide treatment of IscU, and 35S is released by reducing agents. The C-terminal region of IscS (residues 376–413) is important for IscU binding and sulfur transfer. [35S]-cysteine radiotracer studies, surface plasmon resonance, isothermal titration calorimetry, deletion mutagenesis The Journal of biological chemistry High 11577100
2000 IscU and its iron-sulfur complex (IscU-Fe/S) stimulate the ATPase activity of the Hsc66 chaperone up to 480-fold in the presence of the co-chaperone Hsc20. Hsc20 enhances binding of IscU to Hsc66, and IscU and Hsc20 form a direct complex, suggesting Hsc20 aids targeting of IscU to Hsc66. ATPase activity assays, surface plasmon resonance, isothermal titration calorimetry Proceedings of the National Academy of Sciences of the United States of America High 10869428
2000 IscU behaves as a substrate for the Hsc66 chaperone, interacting with the substrate-binding domain: IscU inhibited Hsc66 suppression of rhodanese and citrate synthase aggregation, and ATP destabilizes Hsc66·IscU complexes in a manner expected for Hsp70-substrate complexes. IscU binds the ATPase + beta-sandwich subdomain but not the isolated ATPase domain of Hsc66. Chaperone aggregation suppression assay, calorimetry, surface plasmon resonance, truncation mutant binding studies The Journal of biological chemistry High 11053447
2002 Hsc66 interacts specifically with a region of IscU (residues 99–103, LPPVK) identified by phage display and cellulose-bound peptide array. A synthetic peptide ELPPVKIHC (residues 98–106) stimulates Hsc66 ATPase with similar affinity as native IscU but is not bound by Hsc20 and does not synergistically stimulate Hsc66 with Hsc20, indicating Hsc66 and Hsc20 recognize distinct regions of IscU. Phage display, peptide array, ATPase stimulation assay, peptide-binding domain competition assay The Journal of biological chemistry High 11994302
2004 Crystal structure of HscA substrate-binding domain complexed with IscU-derived peptide ELPPVKIHC at 1.95 Å resolution. The peptide binds in an extended conformation in a hydrophobic cleft in the beta-subdomain, in reverse orientation relative to DnaK–peptide complexes. The alpha-helical subdomain is shifted up to 10 Å relative to DnaK. X-ray crystallography, molecular replacement Journal of molecular biology High 15351650
2004 NMR solution structure of monomeric H. influenzae IscU with zinc bound at the Fe-S cluster assembly site by three cysteines and one histidine. The structure has an alpha-beta sandwich architecture with a three-stranded antiparallel beta-sheet and four alpha-helices. Removal of zinc by chelation results in widespread loss of structure in the apo form. NMR solution structure determination, zinc chelation experiments Journal of molecular biology High 15522305
2006 HscA/HscB co-chaperone system stimulates [2Fe-2S] cluster transfer from IscU to apo-ferredoxin more than 20-fold in an ATP-dependent reaction requiring both HscB and MgATP. No stimulation was observed without HscB or MgATP, establishing that cluster transfer from IscU is an ATP-dependent process. CD and EPR spectrometry to monitor cluster transfer kinetics, phosphate production assay Biochemistry High 16964969
2007 Reductive coupling of two [2Fe-2S]2+ clusters on the IscU homodimer forms a single [4Fe-4S]2+ cluster, demonstrated by UV-visible absorption, Mössbauer, and resonance Raman spectroscopies using dithionite. Isc ferredoxin can also drive partial reductive coupling, suggesting it may be the physiological reductant. UV-visible absorption, Mössbauer spectroscopy, resonance Raman spectroscopy, EPR spectroscopy Biochemistry High 17506525
2007 The [4Fe-4S] cluster-loaded form of IscU, but not the [2Fe-2S] cluster-loaded form, transfers its cluster intact to apo-aconitase A in vitro to activate the enzyme. An Asp39Ala substitution in IscU distinguishes the two cluster-loaded conformers and acts as a dominant-negative inhibitor of wild-type IscU-directed apo-aconitase activation. In vitro aconitase activation assay, mutant IscU inhibition studies Biochemistry High 17506526
2008 Crystal structure of [2Fe-2S]-bound IscU from Aquifex aeolicus at 2.3 Å reveals a novel asymmetric trimer with only one [2Fe-2S] cluster coordinated by Cys36, His106, Cys63, and Cys107 from a single protomer; the cluster is buried at the inter-protomer interface. The three protomers adopt distinct conformations with substantial rearrangement of loops carrying cluster-ligand residues. X-ray crystallography, multiwavelength anomalous diffraction Journal of molecular biology High 18723024
2008 HscA-mediated acceleration of [2Fe-2S] cluster transfer from IscU to apoferredoxin requires both HscB and ATP hydrolysis. A mutant HscA(T212V) lacking ATPase activity cannot accelerate transfer. ATP addition to the HscA/HscB/IscU complex causes a transient distortion of the IscU-bound cluster detectable by CD, linked to HscA conformational change during T→R transition accompanying ATP hydrolysis. Circular dichroism, ATPase activity assay, limiting reagent experiments with HscA T212V mutant Biochemistry High 18986169
2004 IscA acts as an iron donor for Fe-S cluster assembly in IscU under conditions where free iron is limiting (chelated by sodium citrate). IscA binds iron with an association constant of ~3×10^19 M^-1 via invariant Cys-99 and Cys-101 residues. IscA mutants that cannot bind iron fail to deliver iron for IscU cluster assembly. In vitro Fe-S cluster assembly assay under iron-limiting conditions, site-directed mutagenesis of IscA cysteine residues The Journal of biological chemistry High 15247288
2006 Cytosolic human ISCU forms a complex in vitro with cytosolic human ISCS (cysteine desulfurase), and together they facilitate efficient de novo [4Fe-4S] cluster formation on IRP1 when incubated with iron and cysteine, demonstrating that de novo Fe-S cluster biogenesis can occur in the cytosol. In vitro cluster assembly assay on IRP1, 35S radiotracer studies for ISCS desulfurase activity, Pichia pastoris overexpression The Journal of biological chemistry High 16527810
2006 Suppression of human ISCU by RNAi inactivates mitochondrial and cytosolic aconitases in a compartment-specific manner, inappropriately activates iron regulatory proteins (IRP1/IRP2), and disrupts intracellular iron homeostasis, including increased iron uptake. Endogenous ISCU levels are also suppressed by iron deprivation. RNAi knockdown, aconitase enzyme activity assay, IRP RNA-binding assay, iron homeostasis measurements Cell metabolism High 16517407
2009 NMR studies of E. coli IscU show that apo-IscU exists as two distinct slowly-interconverting conformations: one largely disordered (D) and one largely ordered (S) except for metal-binding residues. The S-state is stabilized by zinc or by the D39A substitution. HscB binds preferentially to the S-state of IscU and interacts most with the two N-terminal beta-strands and C-terminal alpha-helix. NMR spectroscopy (chemical shift perturbation), zinc addition experiments, mutant analysis Biochemistry High 19492851
2011 The disordered (D) conformational state of IscU is the preferred substrate for binding to cysteine desulfurase IscS for Fe-S cluster assembly. IscS addition shifts the IscU equilibrium toward the D-state, increasing H/D exchange. IscU variants favoring the S-state show a lag in cluster assembly; those favoring D-state assemble less stable clusters. This establishes functional importance of the S↔D conformational equilibrium. NMR spectroscopy (H/D exchange, chemical shift perturbation), in vitro Fe-S cluster assembly assays with S-state and D-state biased IscU variants Proceedings of the National Academy of Sciences of the United States of America High 22203963
2012 HscA (Hsp70 chaperone) binds preferentially to the disordered (D) conformational state of IscU, while the J-protein HscB binds preferentially to the structured (S) state. HscA-ADP stabilizes the D-state; IscU is released when HscA binds ATP. This defines a chaperone cycle in which cluster transfer is coupled to ATP hydrolysis and IscU D-state stabilization, followed by HscB release. NMR spectroscopy with S-state and D-state biased IscU variants, chaperone interaction studies The Journal of biological chemistry High 22782893
2012 The S↔D conformational interconversion of metamorphic IscU involves concerted trans-to-cis isomerization of two conserved peptidyl-prolyl peptide bonds: N13-P14 and P100-P101. The D-state contains an ordered domain stabilizing two cis peptide bonds while P35 and P100 are trans in the S-state. NMR spectroscopy (chemical shift analysis, NOE measurements for prolyl-peptide bond configuration) Biochemistry High 23110687
2013 Human mtHSP70 (DnaK-type) and NFS1 (cysteine desulfurase) bind preferentially to the disordered (D) state of ISCU, while HSC20 (DnaJ-type) binds preferentially to the structured (S) state. NFS1-ISD11 complex also preferentially binds the D-state. ISD11 does not interact directly with ISCU. [2Fe-2S] and [4Fe-4S] clusters are assembled on ISCU catalyzed by NFS1, at a higher rate with the NFS1-ISD11 complex. NMR spectroscopy with ISCU state-biased variants, ATPase activity assay, in vitro Fe-S cluster assembly assay The Journal of biological chemistry High 23940031
2011 Mammalian frataxin interacts with a preformed ISCU/NFS1/ISD11 core complex (rather than individual components) to form a quaternary complex of ~190 kDa, with ISCU, NFS1, and ISD11 being the main endogenous frataxin interactors. This interaction defines the essential function of frataxin in Fe-S cluster biosynthesis. Co-immunoprecipitation with recombinant frataxin in mammalian cells, heterologous expression of complex components, size-exclusion chromatography PloS one High 21298097
2015 Frataxin enhances the rate of sulfur transfer from NFS1 persulfide to ISCU cysteine C104, leading to persulfide accumulation on ISCU. Frataxin also enhances sulfur transfer to small thiols (DTT, L-cysteine, GSH) from NFS1 persulfide. This reveals frataxin functions as an enhancer of sulfur transfer within the NFS1-ISD11-ISCU complex. Maleimide-peptide probing of cysteine-persulfide combined with mass spectrometry Nature communications High 25597503
2018 FXN (frataxin) tightly binds a single Fe2+ but not Fe3+. FXN does not bind ISCU directly, but both interact with the cysteine desulfurase complex (NIA)2. FXN binds (NIA)2 more strongly in the presence of ISCU. Upon addition of L-cysteine and a reductant (reduced FDX2 or DTT), Fe2+ is released from FXN consistent with Fe2+-FXN being the proximal iron source for Fe-S cluster assembly on ISCU. Isothermal titration calorimetry, multinuclear NMR spectroscopy Journal of inorganic biochemistry High 29576242
2013 mTORC1 associates with ISCU and phosphorylates ISCU at serine 14, stabilizing the ISCU protein. mTORC1 inhibition reduces ISCU levels and prevents Fe-S cluster assembly. Co-immunoprecipitation, in vitro kinase assay, mTORC1 inhibitor treatment, Fe-S cluster assembly readout The Journal of biological chemistry Medium 23508953
2012 HscA/HscB co-chaperone system is required for efficient ATP-dependent [2Fe-2S] cluster transfer from IscU to apo-Grx5 (monothiol glutaredoxin), providing a 700-fold enhancement in transfer rate. This establishes a route for [2Fe-2S] clusters assembled on IscU to be stored and transported by monothiol glutaredoxins. Circular dichroism spectroscopy monitoring cluster transfer, rate measurements ±HscA/HscB/Mg-ATP Journal of the American Chemical Society High 22963613
2012 Three-dimensional NMR structures of E. coli apo-IscU (both wild-type predominantly in S-state and D39A variant >95% S-state) were determined. Hydrophobic residues at position 39 stabilize the S-state by reducing loop flexibility around conserved cysteines. Alanine substitutions at positions 90, 107, and 111 stabilize the protein without affecting loop dynamics. NMR spectroscopy (3D structure determination), systematic mutagenesis, stability measurements Biochemistry High 22734684
2014 ISCU G50E mutation (found in compound heterozygous myopathy patients) results in compromised interaction with sulfur donor NFS1 and the J-protein HSCB, impairing Fe-S cluster synthesis rate. This leads to defects in electron transport chain complexes, loss of cellular respiration, increased mitochondrial iron, and reactive oxygen species. Biochemical interaction assays (NFS1-ISCU, HSCB-ISCU binding), Fe-S cluster synthesis assay, ETC complex activity assays, ROS measurements in human cell lines and yeast models The Journal of biological chemistry High 24573684
2020 ISCU interacts directly with NFU1, with Kd = 1.1 µM (by ITC). The structured conformer of ISCU binds NFU1 via its cluster-binding region interacting with two alpha-helices in the C-terminal domain of NFU1. ISCU[4Fe-4S] transfers its Fe-S cluster to apo-NFU1 in a chaperone-independent manner, while ISCU[2Fe-2S] does not transfer its cluster to NFU1. NMR spectroscopy, small-angle X-ray scattering, isothermal titration calorimetry, size exclusion chromatography, in vitro cluster transfer assay Journal of structural biology High 32151725
2021 Crystal structure of archaeal IscU (Methanothrix thermoacetophila) dimer at atomic resolution shows two [2Fe-2S] clusters facing each other at the dimer interface, with Asp40 serving as a fourth ligand in addition to three Cys residues. His106 is required for reductive coupling of two [2Fe-2S] to one [4Fe-4S] cluster (EPR-confirmed), without structural alteration by H106A substitution, indicating His106's functional role in cluster conversion. X-ray crystallography, EPR spectroscopy, site-directed mutagenesis Biochemistry High 33938220
2022 Iron binds to the assembly site of prokaryotic and eukaryotic ISCU via cysteine residues (1-Cys and 2-Cys forms). The 2-Cys form predominates at pH 8 and correlates with Fe-S cluster assembly activity. X-ray absorption, Mössbauer, NMR, CD, and EPR characterization of the 2-Cys form shows iron is coordinated by four conserved residues (Cys35, Asp37, Cys61, His103) in tetrahedral geometry. An auxiliary non-cysteine iron-binding site in ISCU does not exist. SEC, circular dichroism, Mössbauer, X-ray absorption, NMR, EPR, site-directed mutagenesis Journal of the American Chemical Society High 36121382
2015 p53 transcriptionally activates ISCU expression by binding to an intronic p53-binding site. Knockdown of ISCU enhances IRP1 binding to ferritin heavy chain mRNA's iron-responsive element, reducing ferritin translation and causing iron accumulation. p53-mediated ISCU induction is part of a cellular iron homeostasis response to DNA damage. ChIP for p53 binding, siRNA knockdown of ISCU, IRP1-IRE RNA-binding assay, ferritin translation assay, iron measurement Scientific reports Medium 26560363
2014 In the IscU·IscS complex, IscU retains a folded (structured) conformation as shown by NMR, contradicting proposals that IscS preferentially binds the unstructured form of IscU. Advanced solution NMR directly observes IscU's folded state within the 110 kDa complex. Solution NMR spectroscopy of the IscS-IscU complex Chembiochem Medium 25044349
2018 ISCU variants M108I and D39V populate only the structured (S) conformational state. These variants fail to form cysteine desulfurase complexes containing both frataxin (FXN) and ferredoxin (FDX2) simultaneously; when ISCU(M108I) is present, rdFDX2 addition displaces FXN from the [NIA-ISCU-FXN]2 complex, explaining why FXN cannot stimulate cluster assembly on these fully structured ISCU variants with physiological reductant. NMR titration experiments, in vitro Fe-S cluster assembly assay with DTT vs. reduced FDX2, cysteine desulfurase activity assay Biochemistry High 29406711
2008 A single intronic mutation in ISCU (IVS5+382G>C) strengthens a weak splice acceptor site, causing retention of intronic sequence in ISCU mRNA. This leads to marked reduction of mitochondrial ISCU protein in skeletal muscle, decreased IRP1 activity, and intracellular iron overload in skeletal muscle, establishing a mechanistic link between ISCU scaffold protein deficiency, Fe-S cluster biogenesis failure, and iron dysregulation. Genetic mapping, mRNA splice analysis, western blot for ISCU protein, IRP1 activity assay, iron content measurements in patient muscle American journal of human genetics High 18304497
2008 An intron mutation in ISCU activates cryptic splice sites leading to aberrant mRNA with 100 bp of intron 5, causing a frameshift and premature stop codon. Severe protein deficiency of mitochondrial ISCU is found in homozygous patient skeletal muscle. The phenotype is confirmed as hereditary myopathy with lactic acidosis (HML) mapped to chromosome 12q23.3-24.11. Genetic mapping (lod score 5.26), RT-PCR splice analysis, western blot Human molecular genetics High 18296749
2010 Tissue-specific splicing of the ISCU intron mutation accounts for the skeletal muscle-restricted phenotype in hereditary myopathy with lactic acidosis: the highest level of incorrectly spliced ISCU mRNA is in skeletal muscle while normal splicing predominates in heart. Functional loss of Fe-S cluster-carrying enzymes and iron accumulation occur in muscle but not other tissues. Complete homozygous knockout of ISCU in mice causes early embryonic death. RT-PCR splice analysis across tissues, enzyme activity assays, iron measurement, mouse knockout Human genetics High 21165651
2011 PTBP1 represses defective splicing of ISCU in myopathy patients, dramatically reducing mutant transcripts. IGF2BP1 (which preferentially binds the mutant sequence) and RBM39 shift splicing toward the incorrect form. These splicing factors directly interact with the sequence harboring the ISCU intron mutation. RNA pulldown to identify interacting nuclear factors, splicing reporter assays with siRNA knockdown of individual factors Human mutation Medium 22125086
2012 MyoD-driven muscle differentiation enhances ISCU mRNA mis-splicing in ISCU myopathy patient myoblasts. Oxidative stress (H2O2 treatment or elevated oxygen) further reduces ISCU protein levels in patient cells, an effect preventable by ascorbate pretreatment, indicating that oxidative stress destabilizes the small amounts of correctly spliced ISCU protein produced in patient skeletal muscle. MyoD expression in patient myoblasts, H2O2 and oxygen treatment with western blot for ISCU protein, antioxidant rescue experiments The Journal of biological chemistry Medium 23035118
2023 Excess copper inhibits Fe-S cluster biogenesis through direct binding to ISCU (as well as ISCA1 and ISCA2) proteins, thereby reducing activity of Fe-S cluster-dependent enzymes and disrupting mitochondrial function. ISCU, ISCA1, and ISCA2 were shown to have strong copper-binding activity. In vitro copper-binding assays with recombinant ISCU, cellular Fe-S enzyme activity assays in Wilson's disease model cells (ATP7A-/-, ATP7B KD), mouse model of Wilson's disease Free radical biology & medicine Medium 37225108
2015 Ferredoxin, in conjunction with NADPH and ferredoxin-NADP reductase, transfers electrons to the IscS/IscU complex to support Fe-S cluster assembly in vitro. This trio of electron-transfer partners is sufficient for the reaction, albeit slower than DTT-mediated assembly. Ferredoxin does not interfere with CyaY's inhibitory activity despite overlapping binding sites on IscS. In vitro Fe-S cluster assembly assay using NADPH/FNR/Fdx as physiological reductant Biochimica et biophysica acta Medium 25688831
2019 IscU residue Y3 (strictly conserved) is essential for in vivo Fe-S cluster assembly function. Substitutions at Y3 abolish function by impairing functional interaction with IscS and sulfur transfer between IscS and IscU. A second-site suppressor mutation in IscS (A349V) rescues Y3 substitutions, linking Y3 function to the conformational dynamics of the flexible loop of IscS required for sulfur transfer. In vivo genetic complementation, biochemical sulfur transfer assays, second-site suppressor screen Molecular microbiology High 31532036
2020 In vivo conformational interconversion between D-state and S-state of IscU is required for Fe-S cluster assembly and transfer. IscU single amino acid substitutions that bypass the need for HscA/HscB show enhanced D↔S interconversion in CD spectroscopic studies. IscU variants locked perpetually in either state cannot perform their in vivo role even with the chaperone system present. In vivo genetic bypass assay of chaperone requirement, CD spectroscopy of IscU variants, Zn2+-induced S-state stabilization Molecular microbiology High 33202070
2014 Drosophila p38 pathway substrate MK2 kinase phosphorylates IscU in both Drosophila and mammalian cells, linking the p38 stress response pathway to mitochondrial Fe-S cluster metabolism. In vitro kinase assay identifying IscU as MK2 substrate in Drosophila cells and mammalian cells The Journal of biological chemistry Low 25204651
2025 ISCU sequestrates p53 in the cytoplasm in macrophages, reducing p53 nuclear localization and relieving transcriptional repression of xCT and Arg1, promoting M2 macrophage polarization. Inhibition of ISCU expression repolarizes macrophages and enhances CD8+ T cell cytotoxicity. Co-immunoprecipitation (ISCU-p53), subcellular fractionation, gene expression analysis, macrophage polarization assays, ISCU knockdown in vivo and in vitro Cell death & disease Medium 40541964

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 IscU as a scaffold for iron-sulfur cluster biosynthesis: sequential assembly of [2Fe-2S] and [4Fe-4S] clusters in IscU. Biochemistry 369 10891064
2010 Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 339 20498629
2010 MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PloS one 269 20436681
2006 Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis. Cell metabolism 265 16517407
2001 Transfer of sulfur from IscS to IscU during Fe/S cluster assembly. The Journal of biological chemistry 231 11577100
1999 Functional assignment of the ORF2-iscS-iscU-iscA-hscB-hscA-fdx-ORF3 gene cluster involved in the assembly of Fe-S clusters in Escherichia coli. Journal of biochemistry 228 10544286
2000 Interaction of the iron-sulfur cluster assembly protein IscU with the Hsc66/Hsc20 molecular chaperone system of Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America 193 10869428
2011 Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU/NFS1/ISD11 iron-sulfur assembly complex. PloS one 190 21298097
1999 Hyperproduction of recombinant ferredoxins in escherichia coli by coexpression of the ORF1-ORF2-iscS-iscU-iscA-hscB-hs cA-fdx-ORF3 gene cluster. Journal of biochemistry 173 10393315
2008 Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. American journal of human genetics 165 18304497
1999 Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved gene family for iron-sulfur cluster assembly. Journal of molecular biology 161 10588895
2015 Mammalian frataxin directly enhances sulfur transfer of NFS1 persulfide to both ISCU and free thiols. Nature communications 146 25597503
2007 Formation and properties of [4Fe-4S] clusters on the IscU scaffold protein. Biochemistry 143 17506525
2006 HscA and HscB stimulate [2Fe-2S] cluster transfer from IscU to apoferredoxin in an ATP-dependent reaction. Biochemistry 140 16964969
2006 Iron-sulfur cluster biosynthesis: characterization of Escherichia coli CYaY as an iron donor for the assembly of [2Fe-2S] clusters in the scaffold IscU. The Journal of biological chemistry 139 16603772
2004 Solution NMR structure of the iron-sulfur cluster assembly protein U (IscU) with zinc bound at the active site. Journal of molecular biology 128 15522305
2007 Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. Human molecular genetics 125 17331979
2008 Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect. Human molecular genetics 101 18296749
2002 Hsc66 substrate specificity is directed toward a discrete region of the iron-sulfur cluster template protein IscU. The Journal of biological chemistry 95 11994302
2007 In vitro activation of apo-aconitase using a [4Fe-4S] cluster-loaded form of the IscU [Fe-S] cluster scaffolding protein. Biochemistry 92 17506526
2000 The Fe/S assembly protein IscU behaves as a substrate for the molecular chaperone Hsc66 from Escherichia coli. The Journal of biological chemistry 92 11053447
2015 Regulation of iron homeostasis by the p53-ISCU pathway. Scientific reports 91 26560363
2012 The E. coli SufS-SufE sulfur transfer system is more resistant to oxidative stress than IscS-IscU. FEBS letters 86 23068614
2004 Crystal structure of the molecular chaperone HscA substrate binding domain complexed with the IscU recognition peptide ELPPVKIHC. Journal of molecular biology 85 15351650
2006 Roles of the mammalian cytosolic cysteine desulfurase, ISCS, and scaffold protein, ISCU, in iron-sulfur cluster assembly. The Journal of biological chemistry 83 16527810
2009 Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy. Brain : a journal of neurology 82 19567699
2008 The asymmetric trimeric architecture of [2Fe-2S] IscU: implications for its scaffolding during iron-sulfur cluster biosynthesis. Journal of molecular biology 82 18723024
2008 Studies on the mechanism of catalysis of iron-sulfur cluster transfer from IscU[2Fe2S] by HscA/HscB chaperones. Biochemistry 82 18986169
2004 IscA mediates iron delivery for assembly of iron-sulfur clusters in IscU under the limited accessible free iron conditions. The Journal of biological chemistry 80 15247288
2009 Structure and dynamics of the iron-sulfur cluster assembly scaffold protein IscU and its interaction with the cochaperone HscB. Biochemistry 79 19492851
2004 Regulation of the HscA ATPase reaction cycle by the co-chaperone HscB and the iron-sulfur cluster assembly protein IscU. The Journal of biological chemistry 79 15485839
2002 Iron-sulfur cluster biosynthesis. Thermatoga maritima IscU is a structured iron-sulfur cluster assembly protein. The Journal of biological chemistry 78 11934893
2003 Contributions of the LPPVK motif of the iron-sulfur template protein IscU to interactions with the Hsc66-Hsc20 chaperone system. The Journal of biological chemistry 74 12871959
2012 Monothiol glutaredoxins function in storing and transporting [Fe2S2] clusters assembled on IscU scaffold proteins. Journal of the American Chemical Society 70 22963613
2013 Metamorphic protein IscU alternates conformations in the course of its role as the scaffold protein for iron-sulfur cluster biosynthesis and delivery. FEBS letters 68 23333622
2011 Facilitated transfer of IscU-[2Fe2S] clusters by chaperone-mediated ligand exchange. Biochemistry 67 21977977
2005 Thioredoxin reductase system mediates iron binding in IscA and iron delivery for the iron-sulfur cluster assembly in IscU. The Journal of biological chemistry 67 15985427
2006 Interplay of IscA and IscU in biogenesis of iron-sulfur clusters. The Journal of biological chemistry 65 16877383
2011 Disordered form of the scaffold protein IscU is the substrate for iron-sulfur cluster assembly on cysteine desulfurase. Proceedings of the National Academy of Sciences of the United States of America 64 22203963
2006 Knock-downs of iron-sulfur cluster assembly proteins IscS and IscU down-regulate the active mitochondrion of procyclic Trypanosoma brucei. The Journal of biological chemistry 59 16882667
2005 Multiple turnover transfer of [2Fe2S] clusters by the iron-sulfur cluster assembly scaffold proteins IscU and IscA. The Journal of biological chemistry 58 15964837
2003 Thermotoga maritima IscU. Structural characterization and dynamics of a new class of metallochaperone. Journal of molecular biology 54 12909018
2004 The iron-sulfur cluster assembly genes iscS and iscU of Entamoeba histolytica were acquired by horizontal gene transfer. BMC evolutionary biology 53 15040816
2003 Mitochondrial-type iron-sulfur cluster biosynthesis genes (IscS and IscU) in the apicomplexan Cryptosporidium parvum. Microbiology (Reading, England) 53 14663084
2016 Hypoxia-responsive miR-210 promotes self-renewal capacity of colon tumor-initiating cells by repressing ISCU and by inducing lactate production. Oncotarget 50 27589845
2018 Interactions of iron-bound frataxin with ISCU and ferredoxin on the cysteine desulfurase complex leading to Fe-S cluster assembly. Journal of inorganic biochemistry 49 29576242
2014 The role of zinc in the stability of the marginally stable IscU scaffold protein. Protein science : a publication of the Protein Society 49 24917298
2013 Human mitochondrial chaperone (mtHSP70) and cysteine desulfurase (NFS1) bind preferentially to the disordered conformation, whereas co-chaperone (HSC20) binds to the structured conformation of the iron-sulfur cluster scaffold protein (ISCU). The Journal of biological chemistry 47 23940031
2012 Identification of a signaling axis HIF-1α/microRNA-210/ISCU independent of SDH mutation that defines a subgroup of head and neck paragangliomas. The Journal of clinical endocrinology and metabolism 44 22977270
2015 Ferredoxin, in conjunction with NADPH and ferredoxin-NADP reductase, transfers electrons to the IscS/IscU complex to promote iron-sulfur cluster assembly. Biochimica et biophysica acta 43 25688831
2005 Mobilization of the iron centre in IscA for the iron-sulphur cluster assembly in IscU. The Biochemical journal 42 15828873
2012 Three-dimensional structure and determinants of stability of the iron-sulfur cluster scaffold protein IscU from Escherichia coli. Biochemistry 41 22734684
2004 Bacterial IscU is a well folded and functional single domain protein. European journal of biochemistry 41 15153099
2010 Tissue-specific splicing of ISCU results in a skeletal muscle phenotype in myopathy with lactic acidosis, while complete loss of ISCU results in early embryonic death in mice. Human genetics 40 21165651
2017 MicroRNA-210 Modulates the Cellular Energy Metabolism Shift During H2O2-Induced Oxidative Stress by Repressing ISCU in H9c2 Cardiomyocytes. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 39 29032377
2012 Specialized Hsp70 chaperone (HscA) binds preferentially to the disordered form, whereas J-protein (HscB) binds preferentially to the structured form of the iron-sulfur cluster scaffold protein (IscU). The Journal of biological chemistry 39 22782893
2008 Solution structure of the iron-sulfur cluster cochaperone HscB and its binding surface for the iron-sulfur assembly scaffold protein IscU. Biochemistry 39 18702525
2011 The role of CyaY in iron sulfur cluster assembly on the E. coli IscU scaffold protein. PloS one 38 21799759
2023 Copper exerts cytotoxicity through inhibition of iron-sulfur cluster biogenesis on ISCA1/ISCA2/ISCU assembly proteins. Free radical biology & medicine 34 37225108
2012 Tissue specificity of a human mitochondrial disease: differentiation-enhanced mis-splicing of the Fe-S scaffold gene ISCU renders patient cells more sensitive to oxidative stress in ISCU myopathy. The Journal of biological chemistry 34 23035118
2011 The defective splicing caused by the ISCU intron mutation in patients with myopathy with lactic acidosis is repressed by PTBP1 but can be derepressed by IGF2BP1. Human mutation 33 22125086
2010 Of the vulnerability of orphan complex proteins: the case study of the E. coli IscU and IscS proteins. Protein expression and purification 33 20471481
2003 Iron-sulfur cluster biosynthesis: biochemical characterization of the conformational dynamics of Thermotoga maritima IscU and the relevance for cellular cluster assembly. The Journal of biological chemistry 33 14688265
2021 Quercetin Antagonizes Glucose Fluctuation Induced Renal Injury by Inhibiting Aerobic Glycolysis via HIF-1α/miR-210/ISCU/FeS Pathway. Frontiers in medicine 32 33748166
2011 Three hydrophobic amino acids in Escherichia coli HscB make the greatest contribution to the stability of the HscB-IscU complex. BMC biochemistry 32 21269500
2020 Melatonin Antagonizes Nickel-Induced Aerobic Glycolysis by Blocking ROS-Mediated HIF-1α/miR210/ISCU Axis Activation. Oxidative medicine and cellular longevity 30 32566089
2019 MicroRNA-210 Downregulates ISCU and Induces Mitochondrial Dysfunction and Neuronal Death in Neonatal Hypoxic-Ischemic Brain Injury. Molecular neurobiology 30 30656514
2017 Clinically relevant HIF-1α-dependent metabolic reprogramming in oropharyngeal squamous cell carcinomas includes coordinated activation of CAIX and the miR-210/ISCU signaling axis, but not MCT1 and MCT4 upregulation. Oncotarget 30 28099149
2010 Differences in RNA processing underlie the tissue specific phenotype of ISCU myopathy. Biochimica et biophysica acta 30 20206689
2022 Iron Insertion at the Assembly Site of the ISCU Scaffold Protein Is a Conserved Process Initiating Fe-S Cluster Biosynthesis. Journal of the American Chemical Society 28 36121382
2014 The presence of multiple cellular defects associated with a novel G50E iron-sulfur cluster scaffold protein (ISCU) mutation leads to development of mitochondrial myopathy. The Journal of biological chemistry 28 24573684
2014 Anatomy of an iron-sulfur cluster scaffold protein: Understanding the determinants of [2Fe-2S] cluster stability on IscU. Biochimica et biophysica acta 28 25447544
2017 A novel de novo dominant mutation in ISCU associated with mitochondrial myopathy. Journal of medical genetics 26 29079705
2008 Salmonella enterica requires ApbC function for growth on tricarballylate: evidence of functional redundancy between ApbC and IscU. Journal of bacteriology 25 18441067
2007 Characterization and crystallization of an IscU-type scaffold protein with bound [2Fe-2S] cluster from the hyperthermophile, aquifex aeolicus. Journal of biochemistry 25 17846064
2012 Metamorphic protein IscU changes conformation by cis-trans isomerizations of two peptidyl-prolyl peptide bonds. Biochemistry 24 23110687
2013 Mammalian target of rapamycin complex 1 (mTORC1)-mediated phosphorylation stabilizes ISCU protein: implications for iron metabolism. The Journal of biological chemistry 23 23508953
2021 Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly. International journal of molecular sciences 22 33562493
2021 The Structure of the Dimeric State of IscU Harboring Two Adjacent [2Fe-2S] Clusters Provides Mechanistic Insights into Cluster Conversion to [4Fe-4S]. Biochemistry 22 33938220
2014 The scaffold protein IscU retains a structured conformation in the Fe-S cluster assembly complex. Chembiochem : a European journal of chemical biology 22 25044349
2018 The cold denaturation of IscU highlights structure-function dualism in marginally stable proteins. Communications chemistry 21 35243006
2005 Iron-sulfur cluster biosynthesis. Molecular chaperone DnaK promotes IscU-bound [2Fe-2S] cluster stability and inhibits cluster transfer activity. Biochemistry 20 15766257
2021 A novel role of the mitochondrial iron-sulfur cluster assembly protein ISCU-1/ISCU in longevity and stress response. GeroScience 19 33527323
2018 ISCU(M108I) and ISCU(D39V) Differ from Wild-Type ISCU in Their Failure To Form Cysteine Desulfurase Complexes Containing Both Frataxin and Ferredoxin. Biochemistry 19 29406711
2019 Identification of IscU residues critical for de novo iron-sulfur cluster assembly. Molecular microbiology 17 31532036
2020 ISCU interacts with NFU1, and ISCU[4Fe-4S] transfers its Fe-S cluster to NFU1 leading to the production of holo-NFU1. Journal of structural biology 16 32151725
2022 FDX2 and ISCU Gene Variations Lead to Rhabdomyolysis With Distinct Severity and Iron Regulation. Neurology. Genetics 15 35079622
2018 Zinc(II) binding on human wild-type ISCU and Met140 variants modulates NFS1 desulfurase activity. Biochimie 15 30031876
2015 Functional implications of the interaction between HscB and IscU in the biosynthesis of FeS clusters. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 15 26246371
2014 The p38 pathway regulates oxidative stress tolerance by phosphorylation of mitochondrial protein IscU. The Journal of biological chemistry 14 25204651
2015 Interaction of frataxin, an iron binding protein, with IscU of Fe-S clusters biogenesis pathway and its upregulation in AmpB resistant Leishmania donovani. Biochimie 13 26032732
2015 The Complex Energy Landscape of the Protein IscU. Biophysical journal 12 26331259
2016 Use of antisense oligonucleotides to correct the splicing error in ISCU myopathy patient cell lines. Human molecular genetics 11 28007899
2009 Iron-sulfur cluster biosynthesis: characterization of IscU-IscS complex formation and a structural model for sulfide delivery to the [2Fe-2S] assembly site. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 11 19308466
2025 ISCU-p53 axis orchestrates macrophage polarization to dictate immunotherapy response in esophageal squamous cell carcinoma. Cell death & disease 10 40541964
2020 MiR-210-3p Inhibits Proliferation and Migration of C6 Cells by Targeting Iscu. Neurochemical research 10 32388695
2020 Evidence for dynamic in vivo interconversion of the conformational states of IscU during iron-sulfur cluster biosynthesis. Molecular microbiology 10 33202070
2022 Mechanistic Insights into IscU Conformation Regulation for Fe-S Cluster Biogenesis Revealed by Variable Temperature Electrospray Ionization Native Ion Mobility Mass Spectrometry. Biochemistry 9 36351081
2007 Regulation of the cysteine desulfurase Nfs1 and the scaffold protein IscU in macrophages stimulated with interferon-gamma and lipopolysaccharide. Archives of biochemistry and biophysics 9 17603005
2018 Comparison of the Response of Bacterial IscU and SufU to Zn2+ and Select Transition-Metal Ions. ACS chemical biology 8 29210568

Missed literature

Know a paper Affinage missed for ISCU? Flag it for the maintainers and the community.

No submissions yet.