ArticleNature communications2025
Cryo-EM led analysis of open and closed conformations of Chagas vaccine candidate TcPOP.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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Who cites it
3 citing papers in PubMed.
- Molecular modeling design of antitrypanosomal pyrazolone derivatives targeting Chagas disease: QSAR, docking, molecular dynamics and free energy calculations.Journal of molecular modeling · 2026Article
- Structural basis for dimerization, catalytic regulation, and substrate selectivity of the chloroplast S9D CGEP protease in Arabidopsis thaliana.Protein science : a publication of the Protein Society · 2026Article
- Structural basis for dimerization, catalytic regulation, and substrate selectivity in S9D proteases.bioRxiv : the preprint server for biology · 2026Article
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Authors and funding
14 authors.
Funding
Abstract
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains a significant global public health concern. Despite its profound health impact in both endemic and non-endemic areas, no vaccine is available, and the existing therapies are outdated, producing severe side effects. The 80 kDa prolyl oligopeptidase of Trypanosoma cruzi (TcPOP) has been identified as a leading candidate for Chagas vaccine development. Here we report the three-dimensional structure of TcPOP in open and closed conformation, at a global resolution of 3.8 and 3.6 Å, respectively, determined using single-particle cryo-electron microscopy. Multiple conformations were observed and further characterized using plasmonic optical tweezers and hydrogen-deuterium exchange mass spectrometry. To assess the immunogenic potential of TcPOP, we immunized female mice and evaluated both polyclonal and monoclonal responses against the TcPOP antigen and its homologues. The anti-TcPOP polyclonal response demonstrates invasion blocking properties via parasite lysis. Polyclonal sera were cross-reactive with closely-related POPs but not with human homologues. Collectively, our findings provide structural and functional insights necessary to understand the immunogenicity of TcPOP for future Chagas vaccine development.
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