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CRL2ZER1/ZYG11B recognizes small N-terminal residues for degradation

Author

Listed:
  • Yao Li

    (Tianjin Medical University)

  • Yueling Zhao

    (Tianjin Medical University)

  • Xiaojie Yan

    (Tianjin Medical University)

  • Chen Ye

    (Tianjin Medical University)

  • Sara Weirich

    (University of Stuttgart)

  • Bing Zhang

    (Tianjin Medical University)

  • Xiaolu Wang

    (Tianjin Medical University)

  • Lili Song

    (Tianjin Medical University)

  • Chenhao Jiang

    (Tianjin Medical University)

  • Albert Jeltsch

    (University of Stuttgart)

  • Cheng Dong

    (Tianjin Medical University)

  • Wenyi Mi

    (Tianjin Medical University)

Abstract

N-degron pathway plays an important role in the protein quality control and maintenance of cellular protein homeostasis. ZER1 and ZYG11B, the substrate receptors of the Cullin 2-RING E3 ubiquitin ligase (CRL2), recognize N-terminal (Nt) glycine degrons and participate in the Nt-myristoylation quality control through the Gly/N-degron pathway. Here we show that ZER1 and ZYG11B can also recognize small Nt-residues other than glycine. Specifically, ZER1 binds better to Nt-Ser, -Ala, -Thr and -Cys than to -Gly, while ZYG11B prefers Nt-Gly but also has the capacity to recognize Nt-Ser, -Ala and -Cys in vitro. We found that Nt-Ser, -Ala and -Cys undergo Nt-acetylation catalyzed by Nt-acetyltransferase (NAT), thereby shielding them from recognition by ZER1/ZYG11B in cells. Instead, ZER1/ZYG11B readily targets a selection of small Nt-residues lacking Nt-acetylation for degradation in NAT-deficient cells, implicating its role in the Nt-acetylation quality control. Furthermore, we present the crystal structures of ZER1 and ZYG11B bound to various small Nt-residues and uncover the molecular mechanism of non-acetylated substrate recognition by ZER1 and ZYG11B.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35169-6
    DOI: 10.1038/s41467-022-35169-6
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    References listed on IDEAS

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    1. Eric Linster & Francy L. Forero Ruiz & Pavlina Miklankova & Thomas Ruppert & Johannes Mueller & Laura Armbruster & Xiaodi Gong & Giovanna Serino & Matthias Mann & Rüdiger Hell & Markus Wirtz, 2022. "Cotranslational N-degron masking by acetylation promotes proteome stability in plants," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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    1. Sylvia Varland & Rui Duarte Silva & Ine Kjosås & Alexandra Faustino & Annelies Bogaert & Maximilian Billmann & Hadi Boukhatmi & Barbara Kellen & Michael Costanzo & Adrian Drazic & Camilla Osberg & Kat, 2023. "N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity," Nature Communications, Nature, vol. 14(1), pages 1-27, December.
    2. 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.
    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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