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Oligomerization-primed coiled-coil domain interaction with Ubc13 confers processivity to TRAF6 ubiquitin ligase activity

Author

Listed:
  • Lin Hu

    (Zhejiang University)

  • Jiafeng Xu

    (Zhejiang University)

  • Xiaomei Xie

    (Zhejiang University)

  • Yiwen Zhou

    (Zhejiang University)

  • Panfeng Tao

    (Zhejiang University)

  • Haidong Li

    (Zhejiang University)

  • Xu Han

    (Zhejiang University)

  • Chong Wang

    (Zhejiang University)

  • Jian Liu

    (Zhejiang University)

  • Pinglong Xu

    (Zhejiang University)

  • Dante Neculai

    (Zhejiang University)

  • Zongping Xia

    (Zhejiang University)

Abstract

Ubiquitin ligase TRAF6, together with ubiquitin-conjugating enzyme Ubc13/Uev1, catalyzes processive assembly of unanchored K63-linked polyubiquitin chains for TAK1 activation in the IL-1R/TLR pathways. However, what domain and how it functions to enable TRAF6’s processivity are largely uncharacterized. Here, we find TRAF6 coiled-coil (CC) domain is crucial to enable its processivity. The CC domain mediates TRAF6 oligomerization to ensure efficient long polyubiquitin chain assembly. Mutating or deleting the CC domain impairs TRAF6 oligomerization and processive polyubiquitin chain assembly. Fusion of the CC domain to the E3 ubiquitin ligase CHIP/STUB1 renders the latter capable of NF-κB activation. Moreover, the CC domain, after oligomerization, interacts with Ubc13/Ub~Ubc13, which further contributes to TRAF6 processivity. Point mutations within the CC domain that weaken TRAF6 interaction with Ubc13/Ub~Ubc13 diminish TRAF6 processivity. Our results reveal that the CC oligomerization primes its interaction with Ubc13/Ub~Ubc13 to confer processivity to TRAF6 ubiquitin ligase activity.

Suggested Citation

  • Lin Hu & Jiafeng Xu & Xiaomei Xie & Yiwen Zhou & Panfeng Tao & Haidong Li & Xu Han & Chong Wang & Jian Liu & Pinglong Xu & Dante Neculai & Zongping Xia, 2017. "Oligomerization-primed coiled-coil domain interaction with Ubc13 confers processivity to TRAF6 ubiquitin ligase activity," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01290-0
    DOI: 10.1038/s41467-017-01290-0
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