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It includes amoebic colitis and extraintestinal abscesses.\n                      <jats:italic toggle=\"yes\">E. histolytica<\/jats:italic>\n                      peroxiredoxin (\n                      <jats:italic toggle=\"yes\">Eh<\/jats:italic>\n                      Prx) is a crucial antioxidant enzyme that maintains redox homeostasis and participates in counteracting oxidative stress, supporting trophozoite survival and pathogenicity in the host. We observed the\n                      <jats:italic toggle=\"yes\">Eh<\/jats:italic>\n                      Prx structure to be a decameric ring formed through the polymerization of five dimers.\n                      <jats:italic toggle=\"yes\">Eh<\/jats:italic>\n                      Prx had a unique \u03b1-helical structure at its N-terminus. Protein-protein docking and surface plasmon resonance (SPR) assay results suggest that\n                      <jats:italic toggle=\"yes\">Eh<\/jats:italic>\n                      Prx may bind to myeloid differentiation factor 2 (MD2), the ligand protein of toll-like receptor 4 (TLR4), rather than directly to TLR4. Furthermore,\n                      <jats:italic toggle=\"yes\">Eh<\/jats:italic>\n                      Prx was crucial in the induction of cellular ferroptosis by\n                      <jats:italic toggle=\"yes\">E. histolytica<\/jats:italic>\n                      trophozoites and regulated ferroptosis in host cells through the TLR4\/MD2 pathway. These findings may hold a solid structural basis and promising concepts for investigating the pathogenic mechanisms and drug targets of\n                      <jats:italic toggle=\"yes\">E. histolytica<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Entamoeba histolytica<\/jats:italic>\n                      is the causative agent of amoebiasis, a significant global health concern. Within this parasite,\n                      <jats:italic toggle=\"yes\">E. histolytica<\/jats:italic>\n                      peroxiredoxin (\n                      <jats:italic toggle=\"yes\">Eh<\/jats:italic>\n                      Prx) plays a pivotal role in mitigating oxidative stress, a critical survival mechanism in the hostile environment of the human host.\n                      <jats:italic toggle=\"yes\">Eh<\/jats:italic>\n                      Prx belongs to a family of antioxidant enzymes responsible for detoxifying peroxides, which are deleterious byproducts of cellular metabolism and host-derived immune responses. By neutralizing reactive oxygen species (ROS), EhPrx safeguards the parasite's cellular integrity, ensuring its survival, proliferation, and pathogenicity. Despite its functional importance, the precise structural details of\n                      <jats:italic toggle=\"yes\">Eh<\/jats:italic>\n                      Prx remain elusive, hindering a comprehensive understanding of its molecular mechanisms. Cryo-electron microscopy (cryo-EM) offers a promising avenue for elucidating the high-resolution structure of\n                      <jats:italic toggle=\"yes\">Eh<\/jats:italic>\n                      Prx, which could reveal critical insights into its biological functions and inter- or intramolecular interactions. Such structural characterization may be indispensable for advancing our knowledge of\n                      <jats:italic toggle=\"yes\">E. histolytica<\/jats:italic>\n                      biology and identifying novel diagnostic markers to combat amoebiasis effectively.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00434-26","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:00:40Z","timestamp":1784552440000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Interactions of\n                    <i>Entamoeba histolytica<\/i>\n                    peroxiredoxin with the TLR4\/MD2 complex trigger ferroptosis in host 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