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Two-stage binding of mitochondrial ferredoxin-2 to the core iron-sulfur cluster assembly complex

Author

Listed:
  • Ralf Steinhilper

    (Max Planck Institute of Biophysics)

  • Linda Boß

    (Philipps-Universität Marburg
    Zentrum für Synthetische Mikrobiologie Synmikro)

  • Sven-A. Freibert

    (Philipps-Universität Marburg
    Zentrum für Synthetische Mikrobiologie Synmikro)

  • Vinzent Schulz

    (Philipps-Universität Marburg
    Zentrum für Synthetische Mikrobiologie Synmikro)

  • Nils Krapoth

    (Philipps-Universität Marburg
    Zentrum für Synthetische Mikrobiologie Synmikro)

  • Susann Kaltwasser

    (Max Planck Institute of Biophysics)

  • Roland Lill

    (Philipps-Universität Marburg
    Zentrum für Synthetische Mikrobiologie Synmikro)

  • Bonnie J. Murphy

    (Max Planck Institute of Biophysics)

Abstract

Iron-sulfur (FeS) protein biogenesis in eukaryotes begins with the de novo assembly of [2Fe-2S] clusters by the mitochondrial core iron-sulfur cluster assembly (ISC) complex. This complex comprises the scaffold protein ISCU2, the cysteine desulfurase subcomplex NFS1-ISD11-ACP1, the allosteric activator frataxin (FXN) and the electron donor ferredoxin-2 (FDX2). The structural interaction of FDX2 with the complex remains unclear. Here, we present cryo-EM structures of the human FDX2-bound core ISC complex showing that FDX2 and FXN compete for overlapping binding sites. FDX2 binds in either a ‘distal’ conformation, where its helix F interacts electrostatically with an arginine patch of NFS1, or a ‘proximal’ conformation, where this interaction tightens and the FDX2-specific C terminus binds to NFS1, facilitating the movement of the [2Fe-2S] cluster of FDX2 closer to the ISCU2 FeS cluster assembly site for rapid electron transfer. Structure-based mutational studies verify the contact areas of FDX2 within the core ISC complex.

Suggested Citation

  • Ralf Steinhilper & Linda Boß & Sven-A. Freibert & Vinzent Schulz & Nils Krapoth & Susann Kaltwasser & Roland Lill & Bonnie J. Murphy, 2024. "Two-stage binding of mitochondrial ferredoxin-2 to the core iron-sulfur cluster assembly complex," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54585-4
    DOI: 10.1038/s41467-024-54585-4
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    References listed on IDEAS

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