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Structural bases for the interaction of frataxin with the central components of iron–sulphur cluster assembly

Author

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  • Filippo Prischi

    (National Institute for Medical Research, The Ridgeway)

  • Petr V. Konarev

    (European Molecular Biology Laboratory, EMBL c/o DESY)

  • Clara Iannuzzi

    (National Institute for Medical Research, The Ridgeway)

  • Chiara Pastore

    (National Institute for Medical Research, The Ridgeway)

  • Salvatore Adinolfi

    (National Institute for Medical Research, The Ridgeway)

  • Stephen R. Martin

    (National Institute for Medical Research, The Ridgeway)

  • Dmitri I. Svergun

    (European Molecular Biology Laboratory, EMBL c/o DESY)

  • Annalisa Pastore

    (National Institute for Medical Research, The Ridgeway)

Abstract

Reduced levels of frataxin, an essential protein of as yet unknown function, are responsible for causing the neurodegenerative pathology Friedreich's ataxia. Independent reports have linked frataxin to iron–sulphur cluster assembly through interactions with the two central components of this machinery: desulphurase Nfs1/IscS and the scaffold protein Isu/IscU. In this study, we use a combination of biophysical methods to define the structural bases of the interaction of CyaY (the bacterial orthologue of frataxin) with the IscS/IscU complex. We show that CyaY binds IscS as a monomer in a pocket between the active site and the IscS dimer interface. Recognition does not require iron and occurs through electrostatic interactions of complementary charged residues. Mutations at the complex interface affect the rates of enzymatic cluster formation. CyaY binding strengthens the affinity of the IscS/IscU complex. Our data suggest a new paradigm for understanding the role of frataxin as a regulator of IscS functions.

Suggested Citation

  • Filippo Prischi & Petr V. Konarev & Clara Iannuzzi & Chiara Pastore & Salvatore Adinolfi & Stephen R. Martin & Dmitri I. Svergun & Annalisa Pastore, 2010. "Structural bases for the interaction of frataxin with the central components of iron–sulphur cluster assembly," Nature Communications, Nature, vol. 1(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:1:y:2010:i:1:d:10.1038_ncomms1097
    DOI: 10.1038/ncomms1097
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    Cited by:

    1. 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.

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