FT-GPI, a highly sensitive and accurate predictor of GPI-anchored proteins, reveals the composition and evolution of the GPI proteome in Plasmodium species

Abstract

Background Protozoan parasites are known to attach specific and diverse group of proteins to their plasma membrane via a GPI anchor. In malaria parasites, GPI-anchored proteins (GPI-APs) have been shown to play an important role in host–pathogen interactions and a key function in host cell invasion and immune evasion. Because of their immunogenic properties, some of these proteins have been considered as malaria vaccine candidates. However, identification of all possible GPI-APs encoded by these parasites remains challenging due to their sequence diversity and limitations of the tools used for their characterization. Methods The FT-GPI software was developed to detect GPI-APs based on the presence of a hydrophobic helix at both ends of the premature peptide. FT-GPI was implemented in C ++and applied to study the GPI-proteome of 46 isolates of the order Haemosporida. Using the GPI proteome of Plasmodium falciparum strain 3D7 and Plasmodium vivax strain Sal-1, a heuristic method was defined to select the most sensitive and specific FT-GPI software parameters. Results FT-GPI enabled revision of the GPI-proteome of P. falciparum and P. vivax, including the identification of novel GPI-APs. Orthology- and synteny-based analyses showed that 19 of the 37 GPI-APs found in the order Haemosporida are conserved among Plasmodium species. Our analyses suggest that gene duplication and deletion events may have contributed significantly to the evolution of the GPI proteome, and its composition correlates with speciation. Conclusion FT-GPI-based prediction is a useful tool for mining GPI-APs and gaining further insights into their evolution and sequence diversity. This resource may also help identify new protein candidates for the development of vaccines for malaria and other parasitic diseases.

Apicoplast-derived isoprenoids are essential for biosynthesis of GPI protein anchors, and consequently for egress and invasion inPlasmodium falciparum

“…The C-mannosyltransferase DPY19 is essential for transmission in Plasmodium , but not for asexual blood stage growth so C-mannosylation defects are unlikely to be related to delayed death (25, 26). GPIs function as the membrane anchors for the major surface proteins (GPI-APs) of asexual blood stages as well as being the major class of free glycolipids in the parasite plasma membrane (27, 28). We hypothesise that P. falciparum undergoing PRDD have reduced de novo synthesis of dolichols and consequently less abundant GPI.…”

“…The copyright holder for this preprint this version posted February 15, 2024. ; https://doi.org/10.1101/2024.02.14.580402 doi: bioRxiv preprint well as being the major class of free glycolipids in the parasite plasma membrane (27,28).…”