Structural Insights into Non-canonical Ubiquitination Catalyzed by SidE

Yong Wang, Miao Shi, Han Feng, Yalan Zhu, Songqing Liu, Ang Gao*, Pu Gao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

Ubiquitination constitutes one of the most important signaling mechanisms in eukaryotes. Conventional ubiquitination is catalyzed by the universally conserved E1-E2-E3 three-enzyme cascade in an ATP-dependent manner. The newly identified SidE family effectors of the pathogen Legionella pneumophila ubiquitinate several human proteins by a different mechanism without engaging any of the conventional ubiquitination machinery. We now report the crystal structures of SidE alone and in complex with ubiquitin, NAD, and ADP-ribose, thereby capturing different conformations of SidE before and after ubiquitin and ligand binding. The structures of ubiquitin bound to both mART and PDE domains reveal several unique features of the two reaction steps catalyzed by SidE. Further, the structural and biochemical results demonstrate that SidE family members do not recognize specific structural folds of the substrate proteins. Our studies provide both structural explanations for the functional observations and new insights into the molecular mechanisms of this non-canonical ubiquitination machinery. Structural and biochemical data provide insights into the two-step mechanism by which the SidE family of effector proteins ubiquitinate several human proteins without engaging the canonical ubiquitin machinery.

Original languageEnglish
Pages (from-to)1231-1243.e16
JournalCell
Volume173
Issue number5
DOIs
Publication statusPublished - 17 May 2018
Externally publishedYes

Keywords

  • ADP-ribosylation
  • ADP-ribosyltransferase
  • Legionella pneumophila
  • SdeA
  • SidE
  • host-pathogen interaction
  • phosphodiesterase
  • structure
  • ubiquitin
  • ubiquitination

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Wang, Y., Shi, M., Feng, H., Zhu, Y., Liu, S., Gao, A., & Gao, P. (2018). Structural Insights into Non-canonical Ubiquitination Catalyzed by SidE. Cell, 173(5), 1231-1243.e16. https://doi.org/10.1016/j.cell.2018.04.023