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Modulation of peroxisomal import by the PEX13 SH3 domain and a proximal FxxxF binding motif

Author

Listed:
  • Stefan Gaussmann

    (Bavarian NMR Center and Department of Bioscience
    Institute of Structural Biology)

  • Rebecca Peschel

    (Ruhr University Bochum)

  • Julia Ott

    (Ruhr University Bochum)

  • Krzysztof M. Zak

    (Institute of Structural Biology)

  • Judit Sastre

    (Department of Chemistry)

  • Florent Delhommel

    (Bavarian NMR Center and Department of Bioscience
    Institute of Structural Biology)

  • Grzegorz M. Popowicz

    (Bavarian NMR Center and Department of Bioscience
    Institute of Structural Biology)

  • Job Boekhoven

    (Department of Chemistry)

  • Wolfgang Schliebs

    (Ruhr University Bochum)

  • Ralf Erdmann

    (Ruhr University Bochum)

  • Michael Sattler

    (Bavarian NMR Center and Department of Bioscience
    Institute of Structural Biology)

Abstract

Import of proteins into peroxisomes depends on PEX5, PEX13 and PEX14. By combining biochemical methods and structural biology, we show that the C-terminal SH3 domain of PEX13 mediates intramolecular interactions with a proximal FxxxF motif. The SH3 domain also binds WxxxF peptide motifs in the import receptor PEX5, demonstrating evolutionary conservation of such interactions from yeast to human. Strikingly, intramolecular interaction of the PEX13 FxxxF motif regulates binding of PEX5 WxxxF/Y motifs to the PEX13 SH3 domain. Crystal structures reveal how FxxxF and WxxxF/Y motifs are recognized by a non-canonical surface on the SH3 domain. The PEX13 FxxxF motif also mediates binding to PEX14. Surprisingly, the potential PxxP binding surface of the SH3 domain does not recognize PEX14 PxxP motifs, distinct from its yeast ortholog. Our data show that the dynamic network of PEX13 interactions with PEX5 and PEX14, mediated by diaromatic peptide motifs, modulates peroxisomal matrix import.

Suggested Citation

  • Stefan Gaussmann & Rebecca Peschel & Julia Ott & Krzysztof M. Zak & Judit Sastre & Florent Delhommel & Grzegorz M. Popowicz & Job Boekhoven & Wolfgang Schliebs & Ralf Erdmann & Michael Sattler, 2024. "Modulation of peroxisomal import by the PEX13 SH3 domain and a proximal FxxxF binding motif," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47605-w
    DOI: 10.1038/s41467-024-47605-w
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    References listed on IDEAS

    as
    1. Rini Ravindran & Isabel O. L. Bacellar & Xavier Castellanos-Girouard & Haytham M. Wahba & Zhenghao Zhang & James G. Omichinski & Lydia Kisley & Stephen W. Michnick, 2023. "Peroxisome biogenesis initiated by protein phase separation," Nature, Nature, vol. 617(7961), pages 608-615, May.
    2. Peiqiang Feng & Xudong Wu & Satchal K. Erramilli & Joao A. Paulo & Pawel Knejski & Steven P. Gygi & Anthony A. Kossiakoff & Tom A. Rapoport, 2022. "A peroxisomal ubiquitin ligase complex forms a retrotranslocation channel," Nature, Nature, vol. 607(7918), pages 374-380, July.
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