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Insights into the client protein release mechanism of the ATP-independent chaperone Spy

Author

Listed:
  • Wei He

    (East China University of Science and Technology, Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB))

  • Xinming Li

    (Tsinghua University)

  • Hongjuan Xue

    (Chinese Academy of Sciences)

  • Yuanyuan Yang

    (East China University of Science and Technology, Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB))

  • Jun Mencius

    (East China University of Science and Technology, Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB))

  • Ling Bai

    (East China University of Science and Technology, Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB))

  • Jiayin Zhang

    (East China University of Science and Technology, Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB))

  • Jianhe Xu

    (East China University of Science and Technology, Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB))

  • Bin Wu

    (Chinese Academy of Sciences)

  • Yi Xue

    (Tsinghua University)

  • Shu Quan

    (East China University of Science and Technology, Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB)
    East China University of Science and Technology)

Abstract

Molecular chaperones play a central role in regulating protein homeostasis, and their active forms often contain intrinsically disordered regions (IDRs). However, how IDRs impact chaperone action remains poorly understood. Here, we discover that the disordered N terminus of the prototype chaperone Spy facilitates client release. With NMR spectroscopy and molecular dynamics simulations, we find that the N terminus can bind transiently to the client-binding cavity of Spy primarily through electrostatic interactions mediated by the N-terminal D26 residue. This intramolecular interaction results in a dynamic competition of the N terminus with the client for binding to Spy, which promotes client discharge. Our results reveal the mechanism by which Spy releases clients independent of energy input, thus enriching the current knowledge on how ATP-independent chaperones release their clients and highlighting the importance of synergy between IDRs and structural domains in regulating protein function.

Suggested Citation

  • Wei He & Xinming Li & Hongjuan Xue & Yuanyuan Yang & Jun Mencius & Ling Bai & Jiayin Zhang & Jianhe Xu & Bin Wu & Yi Xue & Shu Quan, 2022. "Insights into the client protein release mechanism of the ATP-independent chaperone Spy," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30499-x
    DOI: 10.1038/s41467-022-30499-x
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    References listed on IDEAS

    as
    1. Kevin Wu & Frederick Stull & Changhan Lee & James C. A. Bardwell, 2019. "Protein folding while chaperone bound is dependent on weak interactions," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    2. Jeremy Weaver & Mengqiu Jiang & Andrew Roth & Jason Puchalla & Junjie Zhang & Hays S. Rye, 2017. "GroEL actively stimulates folding of the endogenous substrate protein PepQ," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
    3. Rebecca Freilich & Miguel Betegon & Eric Tse & Sue-Ann Mok & Olivier Julien & David A. Agard & Daniel R. Southworth & Koh Takeuchi & Jason E. Gestwicki, 2018. "Competing protein-protein interactions regulate binding of Hsp27 to its client protein tau," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
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