Hsp90 and associates shaping parasite biology

Abstract

Hsp90 is a pivotal molecular chaperone involved in maintaining proteostasis and facilitating the maturation of diverse client proteins. Beyond its canonical folding functions, Hsp90 plays non-canonical roles in nuclear trafficking, transcriptional regulation, chromatin remodeling, and DNA repair. These activities are tightly regulated through interactions with specific co-chaperones and through post-translational modifications, collectively forming the “chaperone code.” This study examines Hsp90’s role in thermal adaptation of protozoan parasites when shuttling between the insect and human hosts. Here, we summarize the canonical and diverse non-canonical functions of Hsp90 in three protozoan parasites: Plasmodium , Leishmania , and Trypanosoma . We highlight all the Hsp90 isoforms found in these three parasites and also illustrate all the co-chaperones and post-translational modifications of Hsp90 found to be present in these protozoan parasites. Importantly, the divergence in co-chaperone sequences from human homologs in these parasites presents a promising avenue for targeted antiparasitic drug discovery and development.