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Molecular insights into degron recognition by CRL5ASB7 ubiquitin ligase

Author

Listed:
  • Mengyu Zhou

    (Tianjin Medical University)

  • Xiaolu Wang

    (Tianjin Medical University)

  • Jiangtao Li

    (Tianjin Medical University)

  • Jinfeng Ma

    (Tianjin Medical University)

  • Ziyu Bao

    (Tianjin Medical University)

  • Xiaojie Yan

    (Tianjin Medical University)

  • Bing Zhang

    (Tianjin Medical University)

  • Tong Liu

    (Second Hospital of Tianjin Medical University)

  • Ying Yu

    (Tianjin Medical University)

  • Wenyi Mi

    (Tianjin Medical University)

  • Cheng Dong

    (Tianjin Medical University
    Second Hospital of Tianjin Medical University)

Abstract

The ankyrin (ANK) SOCS box (ASB) family, encompassing ASB1–18, is the largest group of substrate receptors of cullin 5 Ring E3 ubiquitin ligase. Nonetheless, the mechanism of substrate recognition by ASB family proteins has remained largely elusive. Here we present the crystal structure of ASB7-Elongin B-Elongin C ternary complex bound to a conserved helical degron. ASB7 employs its ANK3-6 to form an extended groove, effectively interacting with the internal α-helix-degron through a network of side-chain-mediated electrostatic and hydrophobic interactions. Our structural findings, combined with biochemical and cellular analyses, identify the key residues of the degron motif and ASB7 required for their recognition. This will facilitate the identification of additional physiological substrates of ASB7 by providing a defined degron motif for screening. Furthermore, the structural insights provide a basis for the rational design of compounds that can specifically target ASB7 by disrupting its interaction with its cognate degron.

Suggested Citation

  • Mengyu Zhou & Xiaolu Wang & Jiangtao Li & Jinfeng Ma & Ziyu Bao & Xiaojie Yan & Bing Zhang & Tong Liu & Ying Yu & Wenyi Mi & Cheng Dong, 2024. "Molecular insights into degron recognition by CRL5ASB7 ubiquitin ligase," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50556-x
    DOI: 10.1038/s41467-024-50556-x
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    References listed on IDEAS

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    1. Yao Li & Yueling Zhao & Xiaojie Yan & Chen Ye & Sara Weirich & Bing Zhang & Xiaolu Wang & Lili Song & Chenhao Jiang & Albert Jeltsch & Cheng Dong & Wenyi Mi, 2022. "CRL2ZER1/ZYG11B recognizes small N-terminal residues for degradation," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Lai Xu & Yue Wei & Jerome Reboul & Philippe Vaglio & Tae-Ho Shin & Marc Vidal & Stephen J. Elledge & J. Wade Harper, 2003. "BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3," Nature, Nature, vol. 425(6955), pages 316-321, September.
    3. Xiaolu Wang & Yao Li & Xiaojie Yan & Qing Yang & Bing Zhang & Ying Zhang & Xinxin Yuan & Chenhao Jiang & Dongxing Chen & Quanyan Liu & Tong Liu & Wenyi Mi & Ying Yu & Cheng Dong, 2023. "Recognition of an Ala-rich C-degron by the E3 ligase Pirh2," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
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