Structure of a Shigella effector reveals a new class of ubiquitin ligases

被引：143

作者：

Zhu, Yongqun ^{[1
]}

Li, Hongtao ^{[1
,2
]}

Hu, Liyan ^{[1
]}

Wang, Jiayi ^{[1
]}

Zhou, Yan ^{[1
]}

Pang, Zhimin ^{[1
]}

Liu, Liping ^{[1
]}

Shao, Feng ^{[1
]}

机构：

[1] Natl Inst Biol Sci, Beijing 102206, Peoples R China

[2] Tianjin Univ Commerce, Coll Biotechnol & Food Sci, Tianjin 300134, Peoples R China

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2008年 / 15卷 / 12期

关键词：

D O I：

10.1038/nsmb.1517

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Bacterial pathogens have evolved effector proteins with ubiquitin E3 ligase activities through structural mimicking. Here we report the crystal structure of the Shigella flexneri type III effector IpaH3, a member of the leucine-rich repeat (LRR)-containing bacterial E3 family. The LRR domain is structurally similar to Yersinia pestis YopM and potentially binds to substrates. The structure of the C-terminal E3 domain differs from the typical RING-and HECT-type E3s. IpaH3 synthesizes a Lys48-linked ubiquitin chain, and the reaction requires noncovalent binding between ubiquitin and a specific E2, UbcH5. Free ubiquitin serves as an acceptor for IpaH3-catalyzed ubiquitin transfer. Cys363 within a conserved CXD motif acts as a nucleophile to catalyze ubiquitin transfer through a transthiolation reaction. The D365N mutant is devoid of E3 activities but turns into a potent ubiquitin-E2 thioesterase. Our analysis establishes a structurally and mechanistically distinct class of ubiquitin ligases found exclusively in pathogenic or symbiotic bacteria.

引用

页码：1302 / 1308

页数：7

共 32 条

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