Molecular Cell
Volume 78, Issue 4, 21 May 2020, Pages 641-652.e9
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Article
Threonine ADP-Ribosylation of Ubiquitin by a Bacterial Effector Family Blocks Host Ubiquitination

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Highlights

  • C. violaceum blocks host ubiquitination via the type III effector CteC

  • CteC is an ADP-ribosyltransferase that specifically modifies Ub on T66

  • Threonine ADP-ribosylation of Ub by CteC disrupts host ubiquitin signaling

  • CteC represents a family of bacterial effector proteins that ADP-ribosylate ubiquitin

Summary

Ubiquitination is essential for numerous eukaryotic cellular processes. Here, we show that the type III effector CteC from Chromobacterium violaceum functions as an adenosine diphosphate (ADP)-ribosyltransferase that specifically modifies ubiquitin via threonine ADP-ribosylation on residue T66. The covalent modification prevents the transfer of ubiquitin from ubiquitin-activating enzyme E1 to ubiquitin-conjugating enzyme E2, which inhibits subsequent ubiquitin activation by E2 and E3 enzymes in the ubiquitination cascade and leads to the shutdown of polyubiquitin synthesis in host cells. This unique modification also causes dysfunction of polyubiquitin chains in cells, thereby blocking host ubiquitin signaling. The disruption of host ubiquitination by CteC plays a crucial role in C. violaceum colonization in mice during infection. CteC represents a family of effector proteins in pathogens of hosts from different kingdoms. All the members of this family specifically ADP-ribosylate ubiquitin. The action of CteC reveals a new mechanism for interfering with host ubiquitination by pathogens.

Keywords

ubiquitin
ADP-ribosylation
effector protein
bacterial pathogens
ubiquitination
Chromobacterium violaceum
type III secretion system
NF-κB
posttranslational modification
polyubiquitin chain

Cited by (0)

6

These authors contributed equally

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Present address: Drug Discovery Department, Yangshengtang Group, Hangzhou, Zhejiang 310024, China

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