Cargando…

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

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 t...

Descripción completa

Detalles Bibliográficos
Autores principales: Wei, Congwen, Wang, Ying, Du, Zongmin, Guan, Kai, Cao, Ye, Yang, Huiying, Zhou, Pengyu, Wu, Feixiang, Chen, Jiankang, Wang, Penghao, Zheng, Zirui, Zhang, Pingping, Zhang, Yanhong, Ma, Shengli, Yang, Ruifu, Zhong, Hui, He, Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260993/
https://www.ncbi.nlm.nih.gov/pubmed/27929533
http://dx.doi.org/10.1038/cddis.2016.413
_version_ 1782499497392209920
author Wei, Congwen
Wang, Ying
Du, Zongmin
Guan, Kai
Cao, Ye
Yang, Huiying
Zhou, Pengyu
Wu, Feixiang
Chen, Jiankang
Wang, Penghao
Zheng, Zirui
Zhang, Pingping
Zhang, Yanhong
Ma, Shengli
Yang, Ruifu
Zhong, Hui
He, Xiang
author_facet Wei, Congwen
Wang, Ying
Du, Zongmin
Guan, Kai
Cao, Ye
Yang, Huiying
Zhou, Pengyu
Wu, Feixiang
Chen, Jiankang
Wang, Penghao
Zheng, Zirui
Zhang, Pingping
Zhang, Yanhong
Ma, Shengli
Yang, Ruifu
Zhong, Hui
He, Xiang
author_sort Wei, Congwen
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5260993
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-52609932017-01-26 The Yersinia Type III secretion effector YopM Is an E3 ubiquitin ligase that induced necrotic cell death by targeting NLRP3 Wei, Congwen Wang, Ying Du, Zongmin Guan, Kai Cao, Ye Yang, Huiying Zhou, Pengyu Wu, Feixiang Chen, Jiankang Wang, Penghao Zheng, Zirui Zhang, Pingping Zhang, Yanhong Ma, Shengli Yang, Ruifu Zhong, Hui He, Xiang Cell Death Dis Original Article 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. Nature Publishing Group 2016-12 2016-12-08 /pmc/articles/PMC5260993/ /pubmed/27929533 http://dx.doi.org/10.1038/cddis.2016.413 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Wei, Congwen
Wang, Ying
Du, Zongmin
Guan, Kai
Cao, Ye
Yang, Huiying
Zhou, Pengyu
Wu, Feixiang
Chen, Jiankang
Wang, Penghao
Zheng, Zirui
Zhang, Pingping
Zhang, Yanhong
Ma, Shengli
Yang, Ruifu
Zhong, Hui
He, Xiang
The Yersinia Type III secretion effector YopM Is an E3 ubiquitin ligase that induced necrotic cell death by targeting NLRP3
title The Yersinia Type III secretion effector YopM Is an E3 ubiquitin ligase that induced necrotic cell death by targeting NLRP3
title_full The Yersinia Type III secretion effector YopM Is an E3 ubiquitin ligase that induced necrotic cell death by targeting NLRP3
title_fullStr The Yersinia Type III secretion effector YopM Is an E3 ubiquitin ligase that induced necrotic cell death by targeting NLRP3
title_full_unstemmed The Yersinia Type III secretion effector YopM Is an E3 ubiquitin ligase that induced necrotic cell death by targeting NLRP3
title_short The Yersinia Type III secretion effector YopM Is an E3 ubiquitin ligase that induced necrotic cell death by targeting NLRP3
title_sort yersinia type iii secretion effector yopm is an e3 ubiquitin ligase that induced necrotic cell death by targeting nlrp3
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260993/
https://www.ncbi.nlm.nih.gov/pubmed/27929533
http://dx.doi.org/10.1038/cddis.2016.413
work_keys_str_mv AT weicongwen theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT wangying theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT duzongmin theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT guankai theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT caoye theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT yanghuiying theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT zhoupengyu theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT wufeixiang theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT chenjiankang theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT wangpenghao theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT zhengzirui theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT zhangpingping theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT zhangyanhong theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT mashengli theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT yangruifu theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT zhonghui theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT hexiang theyersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT weicongwen yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT wangying yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT duzongmin yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT guankai yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT caoye yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT yanghuiying yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT zhoupengyu yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT wufeixiang yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT chenjiankang yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT wangpenghao yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT zhengzirui yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT zhangpingping yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT zhangyanhong yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT mashengli yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT yangruifu yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT zhonghui yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3
AT hexiang yersiniatypeiiisecretioneffectoryopmisane3ubiquitinligasethatinducednecroticcelldeathbytargetingnlrp3