A Novel XXXX Binding Domain Mediates Plasma Membrane Localization of ExoU and Other Patatin-like Phospholipases.

@entity796 @entity1078 @entity11763 @entity23559 @entity2631 @entity369
UNASSIGNED: Bacterial toxins require localization to specific intracellular compartments following injection into host cells. In this study, we examine the membrane targeting of a broad family of bacterial proteins, the patatin-like phospholipases. The best-characterized member of this family is ExoU, an effector of the @entity796 type III secretion system. Upon injection into host cells, ExoU localizes to the plasma membrane, where it uses its phospholipase A2 activity to lyse infected cells. The targeting mechanism of ExoU is poorly characterized, but it was recently found to bind to the phospholipid @entity1078 (PI(4,5)P2), a marker for the plasma membrane of eukaryotic cells. We confirmed that the @entity2631 ( @entity2631 ) of ExoU had direct affinity for PI(4,5)P2 and determined that this binding was required for ExoU localization. Previously uncharacterized ExoU homologs from @entity11763 and @entity23559 also localized to the plasma membrane and required PI(4,5)P2 for this localization. A conserved @entity369 within the @entity2631 was critical for interaction of each protein with PI(4,5)P2 and for localization. Further, we determined the crystal structure of the full-length @entity11763 ExoU and found that it was similar to that of @entity796 ExoU. Each @entity2631 contains a four-helical bundle, with the conserved @entity369 exposed at its cap to allow for interaction with the negatively charged PI(4,5)P2. Overall, these findings provide a structural explanation for the targeting of patatin-like phospholipases to the plasma membrane and define the @entity2631 of ExoU as a member of a new class of PI(4,5)P2 binding domains.
