ArticleJournal of the American Chemical Society2020
Molecular Mechanism of ISC Iron-Sulfur Cluster Biogenesis Revealed by High-Resolution Native Mass Spectrometry.
Article in Journal of the American Chemical Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- Intricacies in iron-sulfur cluster function and biogenesis: functional versatility, sulfur sources, and enzyme specificity.RSC chemical biology · 2026Review
- IscS Kinetics in Native Mass Spectrometry Buffers Reveal Key Physiochemical Properties that Influence Enzyme Activity.Journal of the American Society for Mass Spectrometry · 2026Article
- The molecular basis of the synergistic toxicity of nickel and copper, common environmental co-contaminants.Applied and environmental microbiology · 2025Article
- Exploring Metalloproteome Remodeling in Calprotectin-StressedACS chemical biology · 2025Article
- Exploring metalloproteome remodeling in calprotectin-stressedbioRxiv : the preprint server for biology · 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
- A Transcriptomic Study on the Toxic Effects of Iodide (ICurrent issues in molecular biology · 2025Article
- Iron-Sulfur Clusters and Iron Responsive Element Binding Proteins Mediate Iron Accumulation in Corneal Endothelial Cells in Fuchs Dystrophy.Investigative ophthalmology & visual science · 2025Article
- The human zinc-binding cysteine proteome.Cell · 2025Article
- Ferroptosis-immune-metabolic axis in asthma: mechanistic crosstalk, endotype-specific regulation, and translational targeting.Frontiers in immunology · 2025Review
- S-adenosyl-L-methionine is the unexpected methyl donor for the methylation of mercury by the membrane-associated HgcAB complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Proteomic strategies to interrogate the Fe-S proteome.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Structure of a putative immature form of a Rieske-type iron-sulfur protein in complex with zinc chloride.Communications chemistry · 2023Article
- Preparation of Iron-Based Sulfides and Their Applications in Biomedical Fields.Biomimetics (Basel, Switzerland) · 2023Review
- Native mass spectrometric studies of IscSU reveal a concerted, sulfur-initiated mechanism of iron-sulfur cluster assembly.Chemical science · 2022Article
- Article
- 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
- Variable-Temperature Native Mass Spectrometry for Studies of Protein Folding, Stabilities, Assembly, and Molecular Interactions.Annual review of biophysics · 2022Review
- Approaches to Heterogeneity in Native Mass Spectrometry.Chemical reviews · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Iron-sulfur (Fe-S) clusters are ubiquitous protein cofactors that are required for many important biological processes including oxidative respiration, nitrogen fixation, and photosynthesis. Biosynthetic pathways assemble Fe-S clusters with different iron-to-sulfur stoichiometries and distribute these clusters to appropriate apoproteins. In the ISC pathway, the pyridoxal 5'-phosphate-dependent cysteine desulfurase enzyme IscS provides sulfur to the scaffold protein IscU, which templates the Fe-S cluster assembly. Despite their functional importance, mechanistic details for cluster synthesis have remained elusive. Recent advances in native mass spectrometry (MS) have allowed proteins to be preserved in native-like structures and support applications in the investigation of protein structure, dynamics, ligand interactions, and the identification of protein-associated intermediates. Here, we prepared samples under anaerobic conditions and then applied native MS to investigate the molecular mechanism for Fe-S cluster synthesis. This approach was validated by the high agreement between native MS and traditional visible circular dichroism spectroscopic assays. Time-dependent native MS experiments revealed potential iron- and sulfur-based intermediates that decay as the [2Fe-2S] cluster signal developed. Additional experiments establish that (i) Zn(II) binding stabilizes IscU and protects the cysteine residues from oxidation, weakens the interactions between IscU and IscS, and inhibits Fe-S cluster biosynthesis; and (ii) Fe(II) ions bind to the IscU active site cysteine residues and another lower affinity binding site and promote the intermolecular sulfur transfer reaction from IscS to IscU. Overall, these results support an iron-first model for Fe-S cluster synthesis and highlight the power of native MS in defining protein-associated intermediates and elucidating mechanistic details of enzymatic processes.
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