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A conserved N-terminal motif of CUL3 contributes to assembly and E3 ligase activity of CRL3KLHL22

Author

Listed:
  • Weize Wang

    (Peking University Shenzhen Hospital
    Peking University)

  • Ling Liang

    (Peking University Health Science Center)

  • Zonglin Dai

    (Peking University Health Science Center)

  • Peng Zuo

    (Peking University Health Science Center)

  • Shang Yu

    (Peking University Health Science Center)

  • Yishuo Lu

    (Peking University)

  • Dian Ding

    (Peking University Health Science Center)

  • Hongyi Chen

    (Peking University)

  • Hui Shan

    (Peking University Shenzhen Hospital)

  • Yan Jin

    (Peking University Health Science Center)

  • Youdong Mao

    (Peking University
    Peking University)

  • Yuxin Yin

    (Peking University Shenzhen Hospital
    Peking University
    Peking University Health Science Center)

Abstract

The CUL3-RING E3 ubiquitin ligases (CRL3s) play an essential role in response to extracellular nutrition and stress stimuli. The ubiquitin ligase function of CRL3s is activated through dimerization. However, how and why such a dimeric assembly is required for its ligase activity remains elusive. Here, we report the cryo-EM structure of the dimeric CRL3KLHL22 complex and reveal a conserved N-terminal motif in CUL3 that contributes to the dimerization assembly and the E3 ligase activity of CRL3KLHL22. We show that deletion of the CUL3 N-terminal motif impairs dimeric assembly and the E3 ligase activity of both CRL3KLHL22 and several other CRL3s. In addition, we found that the dynamics of dimeric assembly of CRL3KLHL22 generates a variable ubiquitination zone, potentially facilitating substrate recognition and ubiquitination. These findings demonstrate that a CUL3 N-terminal motif participates in the assembly process and provide insights into the assembly and activation of CRL3s.

Suggested Citation

  • Weize Wang & Ling Liang & Zonglin Dai & Peng Zuo & Shang Yu & Yishuo Lu & Dian Ding & Hongyi Chen & Hui Shan & Yan Jin & Youdong Mao & Yuxin Yin, 2024. "A conserved N-terminal motif of CUL3 contributes to assembly and E3 ligase activity of CRL3KLHL22," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48045-2
    DOI: 10.1038/s41467-024-48045-2
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