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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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    1. Ning Zheng & Brenda A. Schulman & Langzhou Song & Julie J. Miller & Philip D. Jeffrey & Ping Wang & Claire Chu & Deanna M. Koepp & Stephen J. Elledge & Michele Pagano & Ronald C. Conaway & Joan W. Con, 2002. "Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex," Nature, Nature, vol. 416(6882), pages 703-709, April.
    2. Lingyan Jin & Kanika Bajaj Pahuja & Katherine E. Wickliffe & Amita Gorur & Christine Baumgärtel & Randy Schekman & Michael Rape, 2012. "Ubiquitin-dependent regulation of COPII coat size and function," Nature, Nature, vol. 482(7386), pages 495-500, February.
    3. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    4. Goran Kokic & Felix R. Wagner & Aleksandar Chernev & Henning Urlaub & Patrick Cramer, 2021. "Structural basis of human transcription–DNA repair coupling," Nature, Nature, vol. 598(7880), pages 368-372, October.
    5. Kuang Shen & Rick K. Huang & Edward J. Brignole & Kendall J. Condon & Max L. Valenstein & Lynne Chantranupong & Aimaiti Bomaliyamu & Abigail Choe & Chuan Hong & Zhiheng Yu & David M. Sabatini, 2018. "Architecture of the human GATOR1 and GATOR1–Rag GTPases complexes," Nature, Nature, vol. 556(7699), pages 64-69, April.
    6. Elijah L. Mena & Predrag Jevtić & Basil J. Greber & Christine L. Gee & Brandon G. Lew & David Akopian & Eva Nogales & John Kuriyan & Michael Rape, 2020. "Structural basis for dimerization quality control," Nature, Nature, vol. 586(7829), pages 452-456, October.
    7. 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.
    8. Stephane Angers & Ti Li & Xianhua Yi & Michael J. MacCoss & Randall T. Moon & Ning Zheng, 2006. "Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machinery," Nature, Nature, vol. 443(7111), pages 590-593, October.
    9. Edward L. Huttlin & Raphael J. Bruckner & Joao A. Paulo & Joe R. Cannon & Lily Ting & Kurt Baltier & Greg Colby & Fana Gebreab & Melanie P. Gygi & Hannah Parzen & John Szpyt & Stanley Tam & Gabriela Z, 2017. "Architecture of the human interactome defines protein communities and disease networks," Nature, Nature, vol. 545(7655), pages 505-509, May.
    10. Jie Chen & Yuhui Ou & Yanyan Yang & Wen Li & Ye Xu & Yuntao Xie & Ying Liu, 2018. "KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing," Nature, Nature, vol. 557(7706), pages 585-589, May.
    11. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    12. Shivesh Kumar & Raul Zavaliev & Qinglin Wu & Ye Zhou & Jie Cheng & Lucas Dillard & Jordan Powers & John Withers & Jinshi Zhao & Ziqiang Guan & Mario J. Borgnia & Alberto Bartesaghi & Xinnian Dong & Pe, 2022. "Structural basis of NPR1 in activating plant immunity," Nature, Nature, vol. 605(7910), pages 561-566, May.
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