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Recognition of an Ala-rich C-degron by the E3 ligase Pirh2

Author

Listed:
  • Xiaolu Wang

    (Tianjin Medical University
    Tianjin Medical University)

  • Yao Li

    (Tianjin Medical University
    Tianjin Medical University)

  • Xiaojie Yan

    (Tianjin Medical University
    Tianjin Medical University)

  • Qing Yang

    (Tianjin Medical University)

  • Bing Zhang

    (Tianjin Medical University)

  • Ying Zhang

    (Tianjin Medical University)

  • Xinxin Yuan

    (Tianjin Medical University)

  • Chenhao Jiang

    (Tianjin Medical University)

  • Dongxing Chen

    (Tianjin Medical University)

  • Quanyan Liu

    (Tianjin Medical University General Hospital)

  • Tong Liu

    (Second Hospital of Tianjin Medical University)

  • Wenyi Mi

    (Tianjin Medical University
    Tianjin Medical University)

  • Ying Yu

    (Tianjin Medical University
    Tianjin Medical University)

  • Cheng Dong

    (Tianjin Medical University
    Tianjin Medical University
    Tianjin Medical University General Hospital
    Second Hospital of Tianjin Medical University)

Abstract

The ribosome-associated quality-control (RQC) pathway degrades aberrant nascent polypeptides arising from ribosome stalling during translation. In mammals, the E3 ligase Pirh2 mediates the degradation of aberrant nascent polypeptides by targeting the C-terminal polyalanine degrons (polyAla/C-degrons). Here, we present the crystal structure of Pirh2 bound to the polyAla/C-degron, which shows that the N-terminal domain and the RING domain of Pirh2 form a narrow groove encapsulating the alanine residues of the polyAla/C-degron. Affinity measurements in vitro and global protein stability assays in cells further demonstrate that Pirh2 recognizes a C-terminal A/S-X-A-A motif for substrate degradation. Taken together, our study provides the molecular basis underlying polyAla/C-degron recognition by Pirh2 and expands the substrate recognition spectrum of Pirh2.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38173-6
    DOI: 10.1038/s41467-023-38173-6
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    References listed on IDEAS

    as
    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. Meenakshi K. Doma & Roy Parker, 2006. "Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation," Nature, Nature, vol. 440(7083), pages 561-564, March.
    3. Yoshitaka Matsuo & Ken Ikeuchi & Yasushi Saeki & Shintaro Iwasaki & Christian Schmidt & Tsuyoshi Udagawa & Fumiya Sato & Hikaru Tsuchiya & Thomas Becker & Keiji Tanaka & Nicholas T. Ingolia & Roland B, 2017. "Ubiquitination of stalled ribosome triggers ribosome-associated quality control," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
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    Cited by:

    1. 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.

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