8H4O
Crystal Structure of nucleotide-free Irgb6_T95D mutant
Summary for 8H4O
| Entry DOI | 10.2210/pdb8h4o/pdb |
| Descriptor | T-cell-specific guanine nucleotide triphosphate-binding protein 2 (2 entities in total) |
| Functional Keywords | toxoplasma gondii, pv, irg, gtpase, hydrolase, immune system |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 2 |
| Total formula weight | 94689.41 |
| Authors | Saijo-Hamano, Y.,Okuma, H.,Sakai, N.,Kato, T.,Imasaki, T.,Nitta, R. (deposition date: 2022-10-11, release date: 2023-10-18, Last modification date: 2024-07-03) |
| Primary citation | Okuma, H.,Saijo-Hamano, Y.,Yamada, H.,Sherif, A.A.,Hashizaki, E.,Sakai, N.,Kato, T.,Imasaki, T.,Kikkawa, S.,Nitta, E.,Sasai, M.,Abe, T.,Sugihara, F.,Maniwa, Y.,Kosako, H.,Takei, K.,Standley, D.M.,Yamamoto, M.,Nitta, R. Structural basis of Irgb6 inactivation by Toxoplasma gondii through the phosphorylation of switch I. Genes Cells, 29:17-38, 2024 Cited by PubMed Abstract: Irgb6 is a priming immune-related GTPase (IRG) that counteracts Toxoplasma gondii. It is known to be recruited to the low virulent type II T. gondii parasitophorous vacuole (PV), initiating cell-autonomous immunity. However, the molecular mechanism by which immunity-related 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 T. gondii 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-free Irgb6-T95D, resulting from a conformational change in the G-domain that allosterically modified the PV membrane-binding interface. In silico docking corroborated the disruption of the physiological membrane binding site. These findings provide novel insights into a T. gondii-induced allosteric inactivation mechanism of Irgb6. PubMed: 37984375DOI: 10.1111/gtc.13080 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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