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

Effectors secreted by the type Ill 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.


Published in:
Nature Structural & Molecular Biology, 23, 9, 847-852
Year:
2016
Publisher:
New York, Nature Publishing Group
ISSN:
1545-9993
Laboratories:




 Record created 2016-10-18, last modified 2018-03-17


Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)