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In this study, we characterize the location and functions of a newly identified thioredoxin in <jats:italic>T. gondii<\/jats:italic>, which was named Trx4.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We characterized the functional role of Trx4 in <jats:italic>T. gondii<\/jats:italic> Type I RH and Type II Pru strains by gene knockout and studied its subcellular localization by endogenous protein HA tagging using CRISPR-Cas9 gene editing. The enzyme-catalyzed proximity labeling technique, the TurboID system, was employed to identify the proteins in proximity to Trx4.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Trx4 was identified as a dense granule protein of <jats:italic>T. gondii<\/jats:italic> predominantly expressed in the parasitophorous vacuole (PV) and was partially co-localized with GRA1 and GRA5. Functional analysis showed that deletion of <jats:italic>trx4<\/jats:italic> markedly influenced the parasite lytic cycle, resulting in impaired host cell invasion capacity in both RH and Pru strains. Mutation of Trx domains in Trx4 in RH strain revealed that two Trx domains were important for the parasite invasion. By utilizing the TurboID system to biotinylate proteins in proximity to Trx4, we identified a substantial number of proteins, some of which are novel, and others are previously characterized, predominantly distributed in the dense granules. In addition, we uncovered three novel proteins co-localized with Trx4. Intriguingly, deletion of <jats:italic>trx4<\/jats:italic> did not affect the localization of these three proteins. Finally, a virulence assay demonstrated that knockout of <jats:italic>trx4<\/jats:italic> resulted in a significant attenuation of virulence and a significant reduction in brain cyst loads in mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Trx4 plays an important role in <jats:italic>T. gondii<\/jats:italic> invasion and virulence in Type I RH strain and Type II Pru strain. Combining the TurboID system with CRISPR-Cas9 technique revealed many PV-localized proximity proteins associated with Trx4. These findings suggest a versatile role of Trx4 in mediating the processes that occur in this distinctive intracellular membrane-bound vacuolar compartment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s13071-024-06259-9","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T15:02:27Z","timestamp":1712242947000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Trx4, a novel thioredoxin protein, is important for Toxoplasma gondii fitness"],"prefix":"10.1186","volume":"17","author":[{"given":"Zhi-Wei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Xiu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hany M.","family":"Elsheikha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Lin","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao-Quan","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Xun","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing-Quan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting-Ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"6259_CR1","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1128\/CMR.05013-11","volume":"25","author":"F Robert-Gangneux","year":"2012","unstructured":"Robert-Gangneux F, Dard\u00e9 ML. 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The corresponding author Prof. Xing-Quan Zhu serves as the Subject Editor for the section \u201cParasite genetics, genomics and proteomics\u201d of Parasites & Vectors.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"178"}}