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Gln40 deamidation blocks structural reconfiguration and activation of SCF ubiquitin ligase complex by Nedd8

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  • Clinton Yu

    (University of California)

  • Haibin Mao

    (University of Washington)

  • Eric J. Novitsky

    (University of California)

  • Xiaobo Tang

    (University of Washington)

  • Scott D. Rychnovsky

    (University of California)

  • Ning Zheng

    (University of Washington)

  • Lan Huang

    (University of California)

Abstract

The full enzymatic activity of the cullin-RING ubiquitin ligases (CRLs) requires a ubiquitin-like protein (that is, Nedd8) modification. By deamidating Gln40 of Nedd8 to glutamate (Q40E), the bacterial cycle-inhibiting factor (Cif) family is able to inhibit CRL E3 activities, thereby interfering with cellular functions. Despite extensive structural studies on CRLs, the molecular mechanism by which Nedd8 Gln40 deamidation affects CRL functions remains unclear. We apply a new quantitative cross-linking mass spectrometry approach to characterize three different types of full-length human Cul1–Rbx1 complexes and uncover major Nedd8-induced structural rearrangements of the CRL1 catalytic core. More importantly, we find that those changes are not induced by Nedd8(Q40E) conjugation, indicating that the subtle change of a single Nedd8 amino acid is sufficient to revert the structure of the CRL catalytic core back to its unmodified form. Our results provide new insights into how neddylation regulates the conformation and activity of CRLs.

Suggested Citation

  • Clinton Yu & Haibin Mao & Eric J. Novitsky & Xiaobo Tang & Scott D. Rychnovsky & Ning Zheng & Lan Huang, 2015. "Gln40 deamidation blocks structural reconfiguration and activation of SCF ubiquitin ligase complex by Nedd8," Nature Communications, Nature, vol. 6(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10053
    DOI: 10.1038/ncomms10053
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