The Yersinia Type III secretion effector YopM Is an E3 ubiquitin ligase that induced necrotic cell death by targeting NLRP3.

Abstract

Yersinia pestis uses type III effector proteins to target eukaryotic signaling systems. The Yersinia outer protein (Yop) M effector from the Y. pestis strain is a critical virulence determinant; however, its role in Y. pestis pathogenesis is just beginning to emerge. Here we first identify YopM as the structural mimic of the bacterial IpaH E3 ligase family in vitro, and establish that the conserved CLD motif in its N-terminal is responsible for the E3 ligase function. Furthermore, we show that NLRP3 is a novel target of the YopM protein. Specially, YopM associates with NLRP3, and its CLD ligase motif mediates the activating K63-linked ubiquitylation of NLRP3; as a result, YopM modulates NLRP3-mediated cell necrosis. Mutation of YopM E3 ligase motif dramatically reduces the ability of Y. pestis to induce HMGB1 release and cell necrosis, which ultimately contributes to bacterial virulence. In conclusion, this study has identified a previously unrecognized role for YopM E3 ligase activity in the regulation of host cell necrosis and plague pathogenesis.

• Authors: Congwen Wei, Ying Wang, Zongmin Du, Kai Guan, Ye Cao, Huiying Yang, Pengyu Zhou, Feixiang Wu, Jiankang Chen, Penghao Wang, Zirui Zheng, Pingping Zhang, Yanhong Zhang, Shengli Ma, Ruifu Yang, Hui Zhong, Xiang He
• Journal: Cell death & disease (Cell Death Dis) Vol. 7 Issue 12 Pg. e2519 (12 08 2016) ISSN: 2041-4889 [Electronic] England
• PMID: 27929533 (Publication Type: Journal Article)

Chemical References

• Bacterial Outer Membrane Proteins
• Bacterial Secretion Systems
• HMGB1 Protein
• NLR Family, Pyrin Domain-Containing 3 Protein
• yopM protein, Yersinia
• Ubiquitin-Protein Ligases
• Lysine

Topics

• Animals
• Bacterial Outer Membrane Proteins (metabolism)
• Bacterial Secretion Systems
• Female
• HEK293 Cells
• HMGB1 Protein (metabolism)
• Humans
• Lysine (metabolism)
• Male
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Necrosis
• Plague (metabolism, microbiology, pathology)
• Protein Binding
• Protein Stability
• Ubiquitin-Protein Ligases (metabolism)
• Ubiquitination
• Virulence
• Yersinia pestis (enzymology, pathogenicity)