Eukaryotic virulence determinants utilize phosphoinositides at the ER and host cell surface

The Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
Trends in Microbiology (Impact Factor: 9.19). 01/2013; 21(3). DOI: 10.1016/j.tim.2012.12.004
Source: PubMed


Similar to bacteria, eukaryotic pathogens may utilize common strategies of pathogenic secretion, because effector proteins from the oomycete Phytophthora infestans and virulence determinants from the human malaria parasite Plasmodium falciparum share a functionally equivalent host-cell-targeting motif (RxLR-dEER in P. infestans and RxLxE/D/Q in P. falciparum). Here we summarize recent studies that reveal that the malarial motif may function differently than previously envisioned. Binding of the lipid phosphatidylinositol 3-phosphate [PI(3)P] is a critical step in accessing the host for both pathogens, but occurs in different locations. Nanomolar affinity for PI(3)P by these short amino acid motifs suggests that a newly identified mechanism of phosphoinositide binding that unexpectedly occurs in secretory locations has been exploited for virulence by diverse eukaryotic pathogens.

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