Structure of Pseudomonas syringae HopZ1a reveals a conserved enzymatic mechanism for YopJ family of Type III effectors
K. MA (1), Z. Zhang (1), W. Ma (1), J. Song (1) (1) University of California Riverside, U.S.A.

Gram negative bacteria inject a plethora of effectors into host cells to compromise immunity. YopJ is a type III effector family that is produced by both animal and plant pathogens. Several YopJ family effectors, including the canonical member YopJ produced by Yersinia spp., and HopZ1a produced by Pseudomonas syringae, act as acetyltransferases. Interestingly, YopJ family effectors are distinctive from the well-characterized lysine acetyltransferases in that they also acetylate serine, threonine and histidine. In addition, YopJ effectors are unique in that they require a eukaryotic cofactor inositol hexakisphosphate (IP6) for activation. In an effort to understand the molecular mechanisms underlying these novel enzymes, we crystallized and determined the structure of HopZ1a in complexes with IP6 and the analog of acetyl group donor (CoA). Our analysis revealed that HopZ1a/IP6 complex is comprised of two closely-packed subdomains with a regulatory domain sitting on top of the catalytic domain. Although the catalytic domain resembles that of ubiquitin-like proteases, association with IP6 alters the overall conformation, allowing the formation of the CoA binding pocket and subsequently activating the acetyltransferase activity. We will report the functional confirmation of key residues interacting with IP6 and CoA. The mechanism of IP6-dependent enzymatic activation and the potential evolution of acetyltransferase activity from ubiquitin-like proteases will also be discussed.

Abstract Number: P9-284
Session Type: Poster