Protozoan HSP90-Heterocomplex: Molecular Interaction Network and Biological Significance

Abstract

The HSP90 chaperone is a highly conserved protein from bacteria to higher eukaryotes. In eukaryotes, this chaperone participates in different large complexes, such as the HSP90 heterocomplex, which has important biological roles in cell homeostasis and differentiation. The HSP90-heterocomplex is also named the HSP90/HSP70 cycle because different co-chaperones (HIP, HSP40, HOP, p23, AHA1, immunophilins, PP5) participate in this complex by assembling sequentially, from the early to the mature complex. In this review, we analyze the conservation and relevance of HSP90 and the HSP90-heterocomplex in several protozoan parasites, with emphasis in Plasmodium spp., Toxoplasma spp., Leishmania spp. and Trypanosoma spp. In the last years, there has been an outburst of studies based on yeast two-hybrid methodology, co-immunoprecipitation-mass spectrometry and bioinformatics, which have generated a most comprehensive protein-protein interaction (PPI) network of HSP90 and its co-chaperones. This review analyzes the existing PPI networks of HSP90 and its co-chaperones of some protozoan parasites and discusses the usefulness of these powerful tools to analyze the biological role of the HSP90-heterocomplex in these parasites. The generation of a T. gondii HSP90 heterocomplex PPI network based on experimental data and a recent Plasmodium HSP90 heterocomplex PPI network are also included and discussed. As an example, the putative implication of nuclear transport and chromatin (histones and Sir2) as HSP90-heterocomplex interactors is here discussed.

Strategies for new and improved vaccines against ticks and tick‐borne diseases

“…In the case of developing vaccines against parasites such as Plasmodium (the causative agent of malaria), Mycobacterium tuberculosis and Toxoplasma (the causative agent of toxoplasmosis), PPIs have shaped the field significantly as it filled major gaps in the knowledge of parasite biology and provided new vaccine targets, screens for parasite-host interactions and defining protective vs. decoy conformational epitopes which may have a tremendous impact on the potential of antigens as protective vaccine candidates (Figure 3) (142)(143)(144)(145)(146)(147)(148)(149)(150)(151). To date, only limited studies on Bm86 have evaluated epitopes as being protective or decoy epitopes (152)(153)(154).…”

Molecular Chaperones ofLeishmania: Central Players in Many Stress-Related and -Unrelated Physiological Processes

“…So far, only limited information exists with regard to the complexes formed by HSP90 and its cochaperones in Leishmania . A comprehensive list of putative components of HSP90-heterocomplexes in several protozoan parasites, including Leishmania has been published recently [ 55 ]. The first experimentally confirmed cochaperone for HSP90 in Leishmania was STI1/HOP [ 56 ].…”

In silico analysis of the HSP90 chaperone system from the African trypanosome, Trypanosoma brucei

“…In Trypanosoma and Leishmania, the HSP90 machinery plays a pivotal role in environmental sensing and life cycle control (Ploeg et al, 1985;Wiesgigl and Clos, 2001;Graefe et al, 2002). In silico analyses of the HSP90/HSPC family of intracellular kinetoplastid parasites has been published (Shonhai et al, 2011;Roy et al, 2012;Figueras et al, 2014;Urményi et al, 2014;Requena et al, 2015), and our study provides an updated and comprehensive analysis for the extracellular parasite, T. brucei. T. brucei exhibits a digenetic lifestyle, and therefore must adapt to fluctuating environmental conditions, such as change in temperature, pH, nutrients, and the pressure from the immune system, as it transitions from the gut of the tsetse fly to the body fluids of its mammalian host (Jones et al, 2008;Roy et al, 2012).…”

“…In all organisms, HSP90 is a dynamic protein that undergoes a conformational cycle that is directionally determined, in large part by ATP binding/hydrolysis, and a cohort of proteins termed co-chaperones (Panaretou et al, 1998;Prodromou, 1999;Johnson and Brown, 2009). The HSP90 co-chaperone system in intracellular protozoan parasites has been explored in previous studies (Seraphim et al, 2013;Figueras et al, 2014). Thus, using the human and trypanosomatid systems, this study analyzed the composition of the T. brucei HSP83 co-chaperone system.…”