ArticleNature chemical biology2025
The ISC machinery assembles [2Fe-2S] clusters by formation and fusion of [1Fe-1S] precursors.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Partial bypass of frataxin deficiency by ISCU M141I restores cytosolic and nuclear Fe-S cluster assembly.Cell death and differentiation · 2026Article
- Linoleic acid accelerates osteoarthritis progression in male rats by targeting iron-sulfur clusters to drive ferroptosis in chondrocytes.Nature communications · 2026Article
- The structure of the SufBCbioRxiv : the preprint server for biology · 2026Article
- Intricacies in iron-sulfur cluster function and biogenesis: functional versatility, sulfur sources, and enzyme specificity.RSC chemical biology · 2026Review
- A Dinuclear Iron(II) Persulfide Complex Reacts with OJournal of the American Chemical Society · 2026Article
- High-Throughput Platform for Discovery of Chemical Inhibitors of Heat Shock Protein 70 (Hsp70): Adaptation for the Specialized Bacterial HscA-HscB-IscU Complex.Chemical biology & drug design · 2026Article
- Regulation of mitochondrial iron homeostasis in tumor cells.Molecular medicine (Cambridge, Mass.) · 2026Review
- Article
- Hydrogen sulfide acts as a sulfur source for iron sulfur cluster biosynthesis in cysteine desulfurase-deficientFrontiers in microbiology · 2026Article
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Authors and funding
12 authors.
Funding
Abstract
Iron-sulfur clusters are essential metallocofactors synthesized by multiprotein machineries via an unclear multistep process. Here we report a step-by-step dissection of the [2Fe-2S] cluster assembly process by the Escherichia coli iron-sulfur cluster (ISC) assembly machinery using an in vitro reconstituted system and a combination of biochemical and spectroscopic techniques. We show that this process is initiated by iron binding to the scaffold protein IscU, which triggers persulfide insertion by the cysteine desulfurase IscS upon the formation of a complex with IscU. Then, the persulfide is cleaved into sulfide by the ferredoxin Fdx, leading to a [1Fe-1S] precursor. IscU dissociates from IscS, dimerizes and generates a bridging [2Fe-2S] cluster by fusion of two [1Fe-1S] precursors. The IscU dimer ultimately dissociates into a monomer, ready to transfer its [2Fe-2S] cluster to acceptors. These data provide a comprehensive description of the [2Fe-2S] cluster assembly process by the ISC assembly machinery, highlighting the formation of key intermediates through a tightly concerted process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.