Structure of a pathogen effector reveals the enzymatic mechanism of a novel acetyltransferase family

Zhang, Zhi Min, Ma, Ka Wai, Yuan, Shuguang, Luo, Youfu, Jiang, Shushu, Hawara, Eva, Pan, Songqin, Ma, Wenbo and Song, Jikui (2016) Structure of a pathogen effector reveals the enzymatic mechanism of a novel acetyltransferase family. Nature Structural and Molecular Biology, 23 (9). pp. 847-852. ISSN 1545-9993

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Effectors secreted by the type III secretion system are essential for bacterial pathogenesis. Members of the Yersinia outer-protein J (YopJ) family of effectors found in diverse plant and animal pathogens depend on a protease-like catalytic triad to acetylate host proteins and produce virulence. However, the structural basis for this noncanonical acetyltransferase activity remains unknown. Here, we report the crystal structures of the YopJ effector HopZ1a, produced by the phytopathogen Pseudomonas syringae, in complex with the eukaryote-specific cofactor inositol hexakisphosphate (IP 6) and/or coenzyme A (CoA). Structural, computational and functional characterizations reveal a catalytic core with a fold resembling that of ubiquitin-like cysteine proteases and an acetyl-CoA-binding pocket formed after IP 6 -induced structural rearrangements. Modeling-guided mutagenesis further identified key IP 6 -interacting residues of Salmonella effector AvrA that are required for acetylating its substrate. Our study reveals the structural basis of a novel class of acetyltransferases and the conserved allosteric regulation of YopJ effectors by IP 6.

Item Type: Article
Additional Information: Funding Information: Acknowledgments This work was supported by funds from a Kimmel Scholar Award from the Sidney Kimmel Foundation for Cancer Research, a University of California Cancer Research Coordination Committee Award (CRC-15-380558) and the March of Dimes Foundation (1-FY15-345) to J.S., and grants from the US NSF (IOS no. 0847870) and the USDA Agriculture Experimental Station Funding (CA-R-PPA-5075-H) to W.M. We thank A. Collmer (Cornell University) for providing the P. syringae strain PtoD28E, D. Maly (University of Washington) for the MKK4 construct and D. Borchardt (UC Riverside) for technical support in NMR and CD spectroscopy.
Uncontrolled Keywords: structural biology,molecular biology ,/dk/atira/pure/subjectarea/asjc/1300/1315
Faculty \ School: Faculty of Science > The Sainsbury Laboratory
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Depositing User: LivePure Connector
Date Deposited: 12 Sep 2022 12:30
Last Modified: 21 Oct 2022 01:41
DOI: 10.1038/nsmb.3279

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