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Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4

Author

Listed:
  • Yusuke Sato

    (The University of Tokyo
    The University of Tokyo
    The University of Tokyo
    Tottori University)

  • Hikaru Tsuchiya

    (Tokyo Metropolitan Institute of Medical Science)

  • Atsushi Yamagata

    (The University of Tokyo
    The University of Tokyo
    The University of Tokyo
    RIKEN Center for Biosystems Dynamics Research)

  • Kei Okatsu

    (The University of Tokyo
    The University of Tokyo)

  • Keiji Tanaka

    (Tokyo Metropolitan Institute of Medical Science)

  • Yasushi Saeki

    (Tokyo Metropolitan Institute of Medical Science)

  • Shuya Fukai

    (The University of Tokyo
    The University of Tokyo
    The University of Tokyo)

Abstract

Npl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast. Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase. Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4-binding motif of Ufd1. The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively. Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains. Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme. This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48–UN complex and its assembly.

Suggested Citation

  • Yusuke Sato & Hikaru Tsuchiya & Atsushi Yamagata & Kei Okatsu & Keiji Tanaka & Yasushi Saeki & Shuya Fukai, 2019. "Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13697-y
    DOI: 10.1038/s41467-019-13697-y
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