Parasite annexins – New molecules with potential for drug and vaccine development

Abstract

In the last few years, annexins have been discovered in several nematodes and other parasites, and distinct differences between the parasite annexins and those of the hosts make them potentially attractive targets for anti-parasite therapeutics. Annexins are ubiquitous proteins found in almost all organisms across all kingdoms.Here, we present an overview of novel annexins from parasitic organisms, and summarize their phylogenetic and biochemical properties, with a view to using them as drug or vaccine targets. Building on structural and biological information that has been accumulated for mammalian and plant annexins, we describe a predicted additional secondary structure element found in many parasite annexins that may confer unique functional properties, and present a specific antigenic epitope for use as a vaccine.

Structure–function analysis of apical membrane‐associated molecules of the tegument of schistosome parasites of humans: prospects for identification of novel targets for parasite control

“…In Sm-Anx-B22, the involvement of Cys 173 in an inter-molecular disulphide bond as well as several intimate electrostatic side chain interactions add to the stabilization of the unique head-to-head dimer topology where the dimer interface is exclusively located in module II/III. Structurally, this is significantly different to other annexin headto-head dimers (Hofmann et al, 2010), where the dimer interface comprises the entire convex surface of both molecules.In addition, from the calcium-bound crystal structure of Sm-Anx-B22, canonical as well as novel calcium binding sites can been identified, which seems to be a recurring motif in parasite annexins. Intriguingly, the dimer arrangement observed in the annexin B22 crystal structure revealed the presence of two non-anticipated prominent features: a potential non-canonical membrane-binding site and a potential binding groove opposite of the former (Figure 4).…”

“…Only one annexin is listed here, although it is known that multiple annexins are present in the tegument of schistosomes. this additional α-helical element on the concave side of the molecule may provide a target for immunological therapeutics (Hofmann et al, 2010). It is tempting to speculate that other parasite annexins with an extended II/III linker peptide may adopt a very similar conformation.…”

“…These findings include (i) immunoreactivity of some parasite annexins (Hongli et al, 2002;Palm et al, 2003;Weiland et al, 2003;Gao et al, 2007;Weeratunga et al, 2012;Leow et al, 2014); (ii) localization of certain parasite annexins to areas of potential exposure and/or structural integrity (Braschi and Wilson, 2006;Jia et al, 2014); and (iii) the existence of a unique structural feature, including the extended helical linker between repeats II and III (Figure 3), in parasite annexins that differentiates them from host annexins (Hofmann et al, 2010;Weeratunga et al, 2012;Leow et al, 2014).…”

Solution Structure, Membrane Interactions, and Protein Binding Partners of the Tetraspanin Sm-TSP-2, a Vaccine Antigen from the Human Blood Fluke Schistosoma mansoni

“…Three have been shown to be promising vaccine antigens, including Sm29 (55), calpain (56), and fructose-bisphosphate aldolase (57). Annexin is also currently under active investigation as a vaccine antigen (58). The susceptibility of schistosomes to vaccines targeting the proteins identified as members of TEMs might indicate that the disruption of the TEMs is an underlying mechanism of the protection afforded by these vaccines.…”

The Relevance of Structural Biology in Studying Molecules Involved in Parasite–Host Interactions: Potential for Designing New Interventions

“…Parasite target proteins involved in structural integrity have been reviewed in detail elsewhere. [9,10] The technique of protein crystallography is poised to deliver much needed insights into the structure-function relationships of key pathogen molecules and their interactions with host proteins. …”