Abstract
SummaryPlasmodium falciparum and Toxoplasma gondii are obligate intracellular parasites that belong to the phylum of Apicomplexa and cause major human diseases. Their access to an intracellular lifestyle is reliant on the coordinated release of proteins from the specialized apical organelles called micronemes and rhoptries. A specific phosphatidic acid effector, the acylated pleckstrin homology domain-containing protein (APH) plays a central role in microneme exocytosis and thus is essential for motility, cell entry, and egress. TgAPH is acylated on the surface of the micronemes and recruited to phosphatidic acid (PA)-enriched membranes. Here, we dissect the atomic details of APH PA-sensing hub and its functional interaction with phospholipid membranes. We unravel the key determinant of PA recognition for the first time and show that APH inserts into and clusters multiple phosphate head-groups at the bilayer binding surface.
Highlights
Apicomplexans form a group of parasitic protists that includes agents of major human diseases: Toxoplasma gondii responsible for toxoplasmosis (Robert-Gangneux and Darde, 2012) and Plasmodium species causing malaria (Bhatt et al, 2015)
The Overall Atomic Structure of T. gondii and P. falciparum acylated pleckstrin homology domain-containing protein (APH) Secondary structure predictions of APHs reveal a highly conserved mixed a/b domain at its C-terminus that is connected to the N-terminal acylation motifs via an extensive linker region (Drozdetskiy et al, 2015) (Figure 1D)
A helical secondary structure is predicted within a charged portion of the APH linker immediately upstream of the augmented pleckstrin homology (PH) domain
Summary
Apicomplexans form a group of parasitic protists that includes agents of major human diseases: Toxoplasma gondii responsible for toxoplasmosis (Robert-Gangneux and Darde, 2012) and Plasmodium species causing malaria (Bhatt et al, 2015). The intracellular lifestyle of apicomplexan parasites (Cowman and Crabb, 2006) is reliant on the actions of proteins released from specialized apical organelles, known as micronemes and rhoptries (Santos and Soldati-Favre, 2011). These apical secretory organelles critically contribute to gliding motility, invasion, and egress from infected cells. Several adhesins are secreted to promote parasite attachment to the target cell and the formation of a moving junction between the cell and the actomyosin system, which drives the parasite inside the host-cell vacuole
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