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Li, Hui, Wang, Jinlong, Kuan, Tung Ariel, Tang, Bozeng, Feng, Li, Wang, Jiuyu, Cheng, Zhi, Skłenar, Jan, Derbyshire, Paul, Hulin, Michelle, Li, Yufei, Zhai, Yi, Hou, Yingnan, Menke, Frank L. H. 
ORCID: https://orcid.org/0000-0003-2490-4824, Wang, Yanli and Ma, Wenbo
(2023)
Pathogen protein modularity enables elaborate mimicry of a host phosphatase.
Cell, 186 (15).
3196-3207.e17.
ISSN 0092-8674
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Abstract
Pathogens produce diverse effector proteins to manipulate host cellular processes. However, how functional diversity is generated in an effector repertoire is poorly understood. Many effectors in the devastating plant pathogen Phytophthora contain tandem repeats of the “(L)WY” motif, which are structurally conserved but variable in sequences. Here, we discovered a functional module formed by a specific (L)WY-LWY combination in multiple Phytophthora effectors, which efficiently recruits the serine/threonine protein phosphatase 2A (PP2A) core enzyme in plant hosts. Crystal structure of an effector-PP2A complex shows that the (L)WY-LWY module enables hijacking of the host PP2A core enzyme to form functional holoenzymes. While sharing the PP2A-interacting module at the amino terminus, these effectors possess divergent C-terminal LWY units and regulate distinct sets of phosphoproteins in the host. Our results highlight the appropriation of an essential host phosphatase through molecular mimicry by pathogens and diversification promoted by protein modularity in an effector repertoire.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding information: W.M. is supported by Gatsby Charitable Foundation, UKRI BBSRC grants BB/W016788/1 and BBS/E/J/000PR9797, and U.S. Department of Agriculture National Institute of Food and Agriculture grant 2018-67014-28488 (jointly offered by the National Science Foundation IOS-1758889). Y.W. is supported by grants from the Natural Science Foundation of China (31930065, 31725008, 22121003, 91940302, 32071444, 32071198, and 31630015), the Chinese Ministry of Science and Technology (2017YFA0504203), and the Chinese Academy of Sciences (XDB37010202). |
| Faculty \ School: | Faculty of Science > The Sainsbury Laboratory Faculty of Science > School of Biological Sciences |
| Depositing User: | LivePure Connector |
| Date Deposited: | 27 Jun 2023 09:31 |
| Last Modified: | 07 May 2024 01:34 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/92505 |
| DOI: | 10.1016/j.cell.2023.05.049 |
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