9HJI

Structure of Trypanosoma cruzi Prolyl Oligopeptidase in the close state

Summary for 9HJI

• Entry DOI: 10.2210/pdb9hji/pdb
• EMDB information: 52215
• Descriptor: Prolyl endopeptidase (1 entity in total)
• Functional Keywords: antigen, chagas disease, prolyl oligopeptidase, hydrolase
• Biological source: Trypanosoma cruzi
• Total number of polymer chains: 1
• Total formula weight: 80362.37

Authors

Batra, S.,Ragan, T.J.,Hesketh, E.,Campeotto, I. (deposition date: 2024-11-29, release date: 2025-10-01)

Primary citation

Batra, S.,Olmo, F.,Ragan, T.J.,Kaplan, M.,Calvaresi, V.,Frank, A.M.,Lancey, C.,Assadipapari, M.,Ying, C.,Struwe, W.B.,Hesketh, E.L.,Kelly, J.M.,Barfod, L.,Campeotto, I.
Cryo-EM led analysis of open and closed conformations of Chagas vaccine candidate TcPOP.
Nat Commun, 16:7164-7164, 2025

PubMed 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profound health impact in both endemic and non-endemic areas, no vaccine is available, and the existing therapies are outdated, producing severe side effects.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.

PubMed: 40764299
DOI: 10.1038/s41467-025-62068-3

Experimental method

ELECTRON MICROSCOPY (3.57 Å)