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Plasmodium falciparum, the causative agent of malaria, employs a diverse array of surface displayed proteins to promote dissemination and establish infection in the human host. Of these, Pf3D7_0606800 is highly immunogenic and has been designated a potential top 10 candidate for inclusion in a multicomponent malarial vaccine. The role of Pf3D7_0606800 in parasite biology, however, is unknown and its characterization has been complicated by a lack of sequence identity with proteins of known structure or function. Towards elucidating Pf3D7_0606800 function, we determined its structure to a resolution of 2.35 Å using selenium single wavelength anomalous dispersion. A bi-lobed architecture displays the core structural hallmarks of Venus Flytrap (VFT) proteins prompting us to re-annotate Pf3D7_0606800 as PfVFT1. Structural analysis further revealed an extended inter-lobe groove that, when interrogated by molecular docking, appears well suited to bind peptide-based ligands. Collectively, our structural characterization of the highly antigenic P. falciparum surface protein PfVFT1 provides intriguing functional insight and establishes a structural template that could prove valuable for malaria vaccine engineering studies.

African trypanosomiasis, caused by parasites of the genus Trypanosoma, is a complex of devastating vector-borne diseases of humans and livestock in sub-Saharan Africa. Central to the pathogenesis of African trypanosomes is their transmission by the arthropod vector, Glossina spp. (tsetse fly). Intriguingly, the efficiency of parasite transmission through the vector is reduced following depletion of Trypanosoma brucei Procyclic-Specific Surface Antigen-2 (TbPSSA-2). To investigate the underlying molecular mechanism of TbPSSA-2, we determined the crystal structures of its ectodomain and that of its homolog T. congolense Insect Stage Antigen (TcISA) to resolutions of 1.65 Å and 2.45 Å, respectively using single wavelength anomalous dispersion. Both proteins adopt a novel bilobed architecture with the individual lobes displaying rotational flexibility around the central tether that suggest a potential mechanism for coordinating a binding partner. In support of this hypothesis, electron density consistent with a bound peptide was observed in the inter-lob cleft of a TcISA monomer. These first reported structures of insect stage transmembrane proteins expressed by African trypanosomes provide potentially valuable insight into the interface between parasite and tsetse vector.