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It is known to be recruited to the low virulent type II <jats:italic>T. gondii<\/jats:italic> parasitophorous vacuole (PV), initiating cell\u2010autonomous immunity. However, the molecular mechanism by which immunity\u2010related GTPases become inactivated after the parasite infection remains obscure. Here, we found that Thr95 of Irgb6 is prominently phosphorylated in response to low virulent type II <jats:italic>T. gondii<\/jats:italic> infection. We observed that a phosphomimetic T95D mutation in Irgb6 impaired its localization to the PV and exhibited reduced GTPase activity in vitro. Structural analysis unveiled an atypical conformation of nucleotide\u2010free Irgb6\u2010T95D, resulting from a conformational change in the G\u2010domain that allosterically modified the PV membrane\u2010binding interface. In silico docking corroborated the disruption of the physiological membrane binding site. These findings provide novel insights into a <jats:italic>T. gondii<\/jats:italic>\u2010induced allosteric inactivation mechanism of Irgb6.<\/jats:p>","DOI":"10.1111\/gtc.13080","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T22:00:00Z","timestamp":1700604000000},"page":"17-38","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural basis of <scp>Irgb6<\/scp> inactivation by <i>Toxoplasma gondii<\/i> through the phosphorylation of switch <scp>I<\/scp>"],"prefix":"10.1111","volume":"29","author":[{"given":"Hiromichi","family":"Okuma","sequence":"first","affiliation":[{"name":"Division of Structural Medicine and Anatomy, Department of Physiology and Cell Biology Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiko","family":"Saijo\u2010Hamano","sequence":"additional","affiliation":[{"name":"Division 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