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Abstract
The oxidative environment of the endoplasmic reticulum (ER) facilitates disulfide bond formation, a process that is critical for correct protein folding. Protein disulfide isomerases (PDIs) are multifunctional ER enzymes that catalyze the formation, cleavage, and rearrangement of disulfide bonds between cysteine residues in their client proteins, stabilizing their structure or modulating their activity. Catalytically active PDIs possess at least one thioredoxin-like domain and facilitate disulfide bond exchange through their conserved CXXC active sites. Toxoplasma gondii, an Apicomplexan parasite, infects an estimated 30% of the world’s population, presenting a significant risk to immunosuppressed individuals and developing fetuses. The fast-growing tachyzoite form of the parasite undergoes a lytic cycle, which causes damage to host tissues and is responsible for the pathogenesis of toxoplasmosis. Although it is estimated that T. gondii contains around 26 PDIs, their distinct roles are still largely unknown. This study examines TgPDIA3, a T. gondii PDI found in the ER, as well as several of its protein substrates. We explore the role of TgPDIA3 in ER redox activity and calcium sequestration and evaluate how these functions impact the parasite’s lytic cycle.