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Molecular basis for the distinct functions of redox-active and FeS-transfering glutaredoxins

Author

Listed:
  • Daniel Trnka

    (Institute for Medical Biochemistry and Molecular Biology, University Medicine, University of Greifswald)

  • Anna D. Engelke

    (Medical Faculty, Heinrich-Heine University Düsseldorf)

  • Manuela Gellert

    (Institute for Medical Biochemistry and Molecular Biology, University Medicine, University of Greifswald)

  • Anna Moseler

    (Institute of Crop Science and Resource Conservation, University of Bonn
    UMR 1136 Interactions Arbres/Microorganismes, Université de Lorraine)

  • Md Faruq Hossain

    (Institute for Medical Biochemistry and Molecular Biology, University Medicine, University of Greifswald)

  • Tobias T. Lindenberg

    (Institute of Neuroanatomy, University Clinics, University of Bonn)

  • Luca Pedroletti

    (Institute of Crop Science and Resource Conservation, University of Bonn)

  • Benjamin Odermatt

    (Institute of Neuroanatomy, University Clinics, University of Bonn)

  • João V. Souza

    (Chemistry, School of Natural and Environmental Sciences, Newcastle University)

  • Agnieszka K. Bronowska

    (Chemistry, School of Natural and Environmental Sciences, Newcastle University)

  • Tobias P. Dick

    (Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ))

  • Uli Mühlenhoff

    (Institute for Cytobiology and Cytopathology, Philipps University Marburg)

  • Andreas J. Meyer

    (Institute of Crop Science and Resource Conservation, University of Bonn)

  • Carsten Berndt

    (Medical Faculty, Heinrich-Heine University Düsseldorf)

  • Christopher Horst Lillig

    (Institute for Medical Biochemistry and Molecular Biology, University Medicine, University of Greifswald)

Abstract

Despite their very close structural similarity, CxxC/S-type (class I) glutaredoxins (Grxs) act as oxidoreductases, while CGFS-type (class II) Grxs act as FeS cluster transferases. Here we show that the key determinant of Grx function is a distinct loop structure adjacent to the active site. Engineering of a CxxC/S-type Grx with a CGFS-type loop switched its function from oxidoreductase to FeS transferase. Engineering of a CGFS-type Grx with a CxxC/S-type loop abolished FeS transferase activity and activated the oxidative half reaction of the oxidoreductase. The reductive half-reaction, requiring the interaction with a second GSH molecule, was enabled by switching additional residues in the active site. We explain how subtle structural differences, mostly depending on the structure of one particular loop, act in concert to determine Grx function.

Suggested Citation

  • Daniel Trnka & Anna D. Engelke & Manuela Gellert & Anna Moseler & Md Faruq Hossain & Tobias T. Lindenberg & Luca Pedroletti & Benjamin Odermatt & João V. Souza & Agnieszka K. Bronowska & Tobias P. Dic, 2020. "Molecular basis for the distinct functions of redox-active and FeS-transfering glutaredoxins," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17323-0
    DOI: 10.1038/s41467-020-17323-0
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    Cited by:

    1. Elizabeth M. Corteselli & Mona Sharafi & Robert Hondal & Maximilian MacPherson & Sheryl White & Ying-Wai Lam & Clarissa Gold & Allison M. Manuel & Albert Vliet & Severin T. Schneebeli & Vikas Anathy &, 2023. "Structural and functional fine mapping of cysteines in mammalian glutaredoxin reveal their differential oxidation susceptibility," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Fabian Geissel & Lukas Lang & Britta Husemann & Bruce Morgan & Marcel Deponte, 2024. "Deciphering the mechanism of glutaredoxin-catalyzed roGFP2 redox sensing reveals a ternary complex with glutathione for protein disulfide reduction," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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