A Pathogen Type III Effector with a Novel E3 Ubiquitin Ligase Architecture

PLoS Pathogens

Alexander U. Singer¹  Xiaohui Xu¹  Tharan Srikumar¹  Lennart Eschen-Lippold¹  Monique Egler²  Sebastian Schulze²  Hong Cui²  Brian Raught²  Dierk Scheel³  Tatiana Skarina³  Justin Lee⁴  Alexei Savchenko⁵  Ulla Bonas⁵ 

[1] Banting and Best Department for Medical Research, University of Toronto, C.H. Best Institute, Toronto, Ontario, Canada;Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada;Department of Genetics, Martin Luther University Halle-Wittenberg, Halle, Germany;Leibniz Institute of Plant Biochemistry, Halle, Germany;Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, MaRS TMDT 9-805, Toronto, Ontario, Canada

关键词: Ubiquitin ligases;    Ubiquitination;    Ligases;    Arabidopsis thaliana;    Leaves;    Cell death;    Crystal structure;    Plant bacterial pathogens;   

DOI  :  10.1371/journal.ppat.1003121

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Type III effectors are virulence factors of Gram-negative bacterial pathogens delivered directly into host cells by the type III secretion nanomachine where they manipulate host cell processes such as the innate immunity and gene expression. Here, we show that the novel type III effector XopL from the model plant pathogen Xanthomonas campestris pv. vesicatoria exhibits E3 ubiquitin ligase activity in vitro and in planta, induces plant cell death and subverts plant immunity. E3 ligase activity is associated with the C-terminal region of XopL, which specifically interacts with plant E2 ubiquitin conjugating enzymes and mediates formation of predominantly K11-linked polyubiquitin chains. The crystal structure of the XopL C-terminal domain revealed a single domain with a novel fold, termed XL-box, not present in any previously characterized E3 ligase. Mutation of amino acids in the central cavity of the XL-box disrupts E3 ligase activity and prevents XopL-induced plant cell death. The lack of cysteine residues in the XL-box suggests the absence of thioester-linked ubiquitin-E3 ligase intermediates and a non-catalytic mechanism for XopL-mediated ubiquitination. The crystal structure of the N-terminal region of XopL confirmed the presence of a leucine-rich repeat (LRR) domain, which may serve as a protein-protein interaction module for ubiquitination target recognition. While the E3 ligase activity is required to provoke plant cell death, suppression of PAMP responses solely depends on the N-terminal LRR domain. Taken together, the unique structural fold of the E3 ubiquitin ligase domain within the Xanthomonas XopL is unprecedented and highlights the variation in bacterial pathogen effectors mimicking this eukaryote-specific activity.

【 授权许可】

CC BY