Global Analysis of Palmitoylated Proteins in Toxoplasma gondii

Post-translational modifications (PTMs) such as palmitoylation are critical for the lytic cycle of the protozoan parasite Toxoplasma gondii. While palmitoylation is involved in invasion, motility, and cell morphology, the proteins that utilize this PTM remain largely unknown. Using a chemical proteomic approach, we report a comprehensive analysis of palmitoylated proteins in T. gondii, identifying a total of 282 proteins, including cytosolic, membrane-associated, and transmembrane proteins. From this large set of palmitoylated targets, we validate palmitoylation of proteins involved in motility (myosin light chain 1, myosin A), cell morphology (PhIL1), and host cell invasion (apical membrane antigen 1, AMA1). Further studies reveal that blocking AMA1 palmitoylation enhances the release of AMA1 and other invasion-related proteins from apical secretory organelles, suggesting a previously unrecognized role for AMA1. These findings suggest that palmitoylation is ubiquitous throughout the T. gondii proteome and reveal insights into the biology of this important human pathogen. [Display omitted] •A Metabolic labeling approach was used to map the palmitome in Toxoplasma gondii•Palmitoylation in T. gondii tachyzoites is highly prevalent•Many components of the parasite’s motility complex (glideosome) are palmitoylated•AMA1 is palmitoylated, and its palmitoylation regulates microneme secretion Palmitoylation is a lipid-derived post-translational modification (PTM). Foe et al. report a comprehensive analysis of palmitoylated proteins in Toxoplasma gondii. They demonstrate that palmitoylation is associated with diverse aspects of T. gondii biology, including motility and morphology, and reveal a function for this PTM in regulating the invasion-associated protein, AMA1.