Browsing by Subject "Host-targeting"

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    Eukaryotic virulence determinants utilize phosphoinositides at the ER and host cell surface
    (Elsevier, 2013) Jiang, Rays H. Y.; Stahelin, Robert V.; Bhattacharjee, Souvik; Haldar, Kasturi; Biochemistry and Molecular Biology, School of Medicine
    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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    Host-targeting of virulence determinants and phosphoinositides in blood stage malaria parasites
    (Elsevier, 2012) Bhattacharjee, Souvik; Stahelin, Robert V.; Haldar, Kasturi; Biochemistry and Molecular Biology, School of Medicine
    Blood stage malaria parasites target a 'secretome' of hundreds of proteins including virulence determinants containing a host (cell) targeting (HT) signal, to human erythrocytes. Recent studies reveal that the export mechanism is due to the HT signal binding to the lipid phosphatidylinositol-3-phosphate [PI(3)P] in the parasite endoplasmic reticulum (ER). An aspartic protease plasmepsin V which cleaves a specialized form of the HT signal was previously thought to be the export mechanism, but is now recognized as a dedicated peptidase that cleaves the signal anchor subsequent to PI(3)P binding. We discuss a model of PI(3)P-dependent targeting and PI(3)P biology of a major human pathogen.