The luminal domain of sortilin adopts a ring-shaped structure exhibiting motifs specific to apicomplexan parasites.

Rhoptries and micronemes are essential for host cell invasion and survival of all apicomplexan parasites, which are composed of numerous obligate intracellular protozoan pathogens including (malaria) and (toxoplasmosis) that infect humans and animals causing severe diseases. We identified SORT as an essential cargo receptor, which drives the transport of rhoptry (ROP) and microneme (MIC) proteins to ensure the biogenesis of these secretory organelles. The luminal domain of 752 amino acid long situated at the N-terminus end of TgSORT has been described to bind to MIC and ROP proteins. Here, we present an optimized protocol for expression of the entire luminal N-terminus of TgSORT (Tg-NSORT) in the yeast . Optimization of its coding sequence, cloning and transformation of the yeast allowed the secretion of Tg-NSORT. The protein was purified and further analyzed by negative staining electron microscopy. In addition, molecular modeling using AlphaFold identified key differences between the human and the sortilin. The structural features that are only present in and other apicomplexan parasites were highlighted. Elucidating the roles of these specific structural features may be useful for designing new therapeutic agents against apicomplexan parasites.