title: Structure of a pathogen effector reveals the enzymatic mechanism of a novel acetyltransferase family.
abstract: 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 (IP6) 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 IP6-induced structural rearrangements. Modeling-guided mutagenesis further identified key IP6-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 IP6.
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, California, USA.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Zhang
authors.affiliation: Department of Plant Pathology and Microbiology, University of California, Riverside, Riverside, California, USA.
authors.forename: Ka-Wai
authors.initials: KW
authors.lastname: Ma
authors.affiliation: Laboratory of Physical Chemistry of Polymers and Membranes, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Shuguang
authors.identifier: 0000-0001-9858-4742
authors.initials: S
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Youfu
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Plant Pathology and Microbiology, University of California, Riverside, Riverside, California, USA.
authors.forename: Shushu
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Plant Pathology and Microbiology, University of California, Riverside, Riverside, California, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Hawara
authors.affiliation: Center for Plant Cell Biology, University of California, Riverside, Riverside, California, USA.
authors.forename: Songqin
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Plant Pathology and Microbiology, University of California, Riverside, Riverside, California, USA.|Center for Plant Cell Biology, University of California, Riverside, Riverside, California, USA.|Institute of Integrative Genome Biology, University of California, Riverside, Riverside, California, USA.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, California, USA.
authors.forename: Jikui
authors.initials: J
authors.lastname: Song
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry*; D000494:Allosteric Regulation; D029681:Arabidopsis Proteins / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D003065:Coenzyme A / Q000737:chemistry; D018360:Crystallography, X-Ray; D054884:Host-Pathogen Interactions; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010833:Phytic Acid / Q000737:chemistry; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D044224:Pseudomonas syringae / Q000201:enzymology
chemical_list: D029681:Arabidopsis Proteins; D001426:Bacterial Proteins; D010833:Phytic Acid; D000123:Acetyltransferases; D003065:Coenzyme A