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Multi-site-mediated entwining of the linear WIR-motif around WIPI β-propellers for autophagy

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Listed:
  • Jinqi Ren

    (Chinese Academy of Sciences)

  • Ruobing Liang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Wenjuan Wang

    (Chinese Academy of Sciences)

  • Dachuan Zhang

    (Tsinghua University)

  • Li Yu

    (Tsinghua University)

  • Wei Feng

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

WIPI proteins (WIPI1-4) are mammalian PROPPIN family phosphoinositide effectors essential for autophagosome biogenesis. In addition to phosphoinositides, WIPI proteins can recognize a linear WIPI-interacting-region (WIR)-motif, but the underlying mechanism is poorly understood. Here, we determine the structure of WIPI3 in complex with the WIR-peptide from ATG2A. Unexpectedly, the WIR-peptide entwines around the WIPI3 seven-bladed β-propeller and binds to three sites in blades 1–3. The N-terminal part of the WIR-peptide forms a short strand that augments the periphery of blade 2, the middle segment anchors into an inter-blade hydrophobic pocket between blades 2–3, and the C-terminal aromatic tail wedges into another tailored pocket between blades 1–2. Mutations in three peptide-binding sites disrupt the interactions between WIPI3/4 and ATG2A and impair the ATG2A-mediated autophagic process. Thus, WIPI proteins recognize the WIR-motif by multi-sites in multi-blades and this multi-site-mediated peptide-recognition mechanism could be applicable to other PROPPIN proteins.

Suggested Citation

  • Jinqi Ren & Ruobing Liang & Wenjuan Wang & Dachuan Zhang & Li Yu & Wei Feng, 2020. "Multi-site-mediated entwining of the linear WIR-motif around WIPI β-propellers for autophagy," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16523-y
    DOI: 10.1038/s41467-020-16523-y
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    Cited by:

    1. Daniel Mann & Simon A. Fromm & Antonio Martinez-Sanchez & Navin Gopaldass & Ramona Choy & Andreas Mayer & Carsten Sachse, 2023. "Atg18 oligomer organization in assembled tubes and on lipid membrane scaffolds," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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