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Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex

Author

Listed:
  • Michal T. Boniecki

    (University of Saskatchewan)

  • Sven A. Freibert

    (Institut für Zytobiologie und Zytopathologie, Philipps-Universität)

  • Ulrich Mühlenhoff

    (Institut für Zytobiologie und Zytopathologie, Philipps-Universität)

  • Roland Lill

    (Institut für Zytobiologie und Zytopathologie, Philipps-Universität
    LOEWE Zentrum für Synthetische Mikrobiologie SynMikro)

  • Miroslaw Cygler

    (University of Saskatchewan
    McGill University)

Abstract

Iron–sulfur (Fe/S) clusters are essential protein cofactors crucial for many cellular functions including DNA maintenance, protein translation, and energy conversion. De novo Fe/S cluster synthesis occurs on the mitochondrial scaffold protein ISCU and requires cysteine desulfurase NFS1, ferredoxin, frataxin, and the small factors ISD11 and ACP (acyl carrier protein). Both the mechanism of Fe/S cluster synthesis and function of ISD11-ACP are poorly understood. Here, we present crystal structures of three different NFS1-ISD11-ACP complexes with and without ISCU, and we use SAXS analyses to define the 3D architecture of the complete mitochondrial Fe/S cluster biosynthetic complex. Our structural and biochemical studies provide mechanistic insights into Fe/S cluster synthesis at the catalytic center defined by the active-site Cys of NFS1 and conserved Cys, Asp, and His residues of ISCU. We assign specific regulatory rather than catalytic roles to ISD11-ACP that link Fe/S cluster synthesis with mitochondrial lipid synthesis and cellular energy status.

Suggested Citation

  • Michal T. Boniecki & Sven A. Freibert & Ulrich Mühlenhoff & Roland Lill & Miroslaw Cygler, 2017. "Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01497-1
    DOI: 10.1038/s41467-017-01497-1
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    Cited by:

    1. M. Tanvir Rahman & M. Kristian Koski & Joanna Panecka-Hofman & Werner Schmitz & Alexander J. Kastaniotis & Rebecca C. Wade & Rik K. Wierenga & J. Kalervo Hiltunen & Kaija J. Autio, 2023. "An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Vinzent Schulz & Ralf Steinhilper & Jonathan Oltmanns & Sven-A. Freibert & Nils Krapoth & Uwe Linne & Sonja Welsch & Maren H. Hoock & Volker Schünemann & Bonnie J. Murphy & Roland Lill, 2024. "Mechanism and structural dynamics of sulfur transfer during de novo [2Fe-2S] cluster assembly on ISCU2," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Sven-A. Freibert & Michal T. Boniecki & Claudia Stümpfig & Vinzent Schulz & Nils Krapoth & Dennis R. Winge & Ulrich Mühlenhoff & Oliver Stehling & Miroslaw Cygler & Roland Lill, 2021. "N-terminal tyrosine of ISCU2 triggers [2Fe-2S] cluster synthesis by ISCU2 dimerization," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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