ArticleNature communications2021
N-terminal tyrosine of ISCU2 triggers [2Fe-2S] cluster synthesis by ISCU2 dimerization.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- Article
- The cytochrome oxidase defect in ISC-depleted yeast is caused by impaired iron-sulfur cluster maturation of the mitoribosome assembly factor Rsm22.FEBS letters · 2025Article
- D-cysteine impairs tumour growth by inhibiting cysteine desulfurase NFS1.Nature metabolism · 2025Article
- The Single Nucleotide Substitution T → A rs2072580 Damages the CREB1 Binding Site in the BidirectionalGenes · 2025Article
- The ISC machinery assembles [2Fe-2S] clusters by formation and fusion of [1Fe-1S] precursors.Nature chemical biology · 2025Article
- How to build a [2Fe-2S] cluster.Nature chemical biology · 2025Article
- Identification of a Selective Inhibitor of Human NFS1, a Cysteine Desulfurase Involved in Fe-S Cluster Assembly, via Structure-Based Virtual Screening.International journal of molecular sciences · 2025Article
- Two-stage binding of mitochondrial ferredoxin-2 to the core iron-sulfur cluster assembly complex.Nature communications · 2024Article
- Defects in the Maturation of Mitochondrial Iron-Sulfur Proteins: Biophysical Investigation of the MMDS3 Causing Gly104Cys Variant of IBA57.International journal of molecular sciences · 2024Article
- Multi-layered metabolic effects of trehalose on the liver proteome in apoE-knockout mice model of liver steatosis.Pharmacological reports : PR · 2024Article
- Mechanism and structural dynamics of sulfur transfer during de novo [2Fe-2S] cluster assembly on ISCU2.Nature communications · 2024Article
- Haptoglobin buffers lipopolysaccharides to delay activation of NFκB.Frontiers in immunology · 2024Article
- Structure of a putative immature form of a Rieske-type iron-sulfur protein in complex with zinc chloride.Communications chemistry · 2023Article
- Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway.Journal of molecular biology · 2023Article
- Functional spectrum and specificity of mitochondrial ferredoxins FDX1 and FDX2.Nature chemical biology · 2023Article
- Iron-dependent post transcriptional control of mitochondrial aconitase expression.Metallomics : integrated biometal science · 2023Article
- A novel IBA57 variant is associated with mitochondrial iron-sulfur protein deficiency and necrotizing myelopathy in dogs.Frontiers in genetics · 2023Article
- Characteristics of the Isu1 C-terminus in relation to [2Fe-2S] cluster assembly and ISCU Myopathy.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2022Article
- 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 · 2022Article
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Synthesis of iron-sulfur (Fe/S) clusters in living cells requires scaffold proteins for both facile synthesis and subsequent transfer of clusters to target apoproteins. The human mitochondrial ISCU2 scaffold protein is part of the core ISC (iron-sulfur cluster assembly) complex that synthesizes a bridging [2Fe-2S] cluster on dimeric ISCU2. Initial iron and sulfur loading onto monomeric ISCU2 have been elucidated biochemically, yet subsequent [2Fe-2S] cluster formation and dimerization of ISCU2 is mechanistically ill-defined. Our structural, biochemical and cell biological experiments now identify a crucial function of the universally conserved N-terminal Tyr35 of ISCU2 for these late reactions. Mixing two, per se non-functional ISCU2 mutant proteins with oppositely charged Asp35 and Lys35 residues, both bound to different cysteine desulfurase complexes NFS1-ISD11-ACP, restores wild-type ISCU2 maturation demonstrating that ionic forces can replace native Tyr-Tyr interactions during dimerization-induced [2Fe-2S] cluster formation. Our studies define the essential mechanistic role of Tyr35 in the reaction cycle of de novo mitochondrial [2Fe-2S] cluster synthesis.
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