8H4O

Crystal Structure of nucleotide-free Irgb6_T95D mutant

8H4O の概要

• エントリーDOI: 10.2210/pdb8h4o/pdb
• 分子名称: T-cell-specific guanine nucleotide triphosphate-binding protein 2 (2 entities in total)
• 機能のキーワード: toxoplasma gondii, pv, irg, gtpase, hydrolase, immune system
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 94689.41

構造登録者

Saijo-Hamano, Y.,Okuma, H.,Sakai, N.,Kato, T.,Imasaki, T.,Nitta, R. (登録日: 2022-10-11, 公開日: 2023-10-18, 最終更新日: 2024-07-03)

主引用文献

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

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: 37984375
DOI: 10.1111/gtc.13080

実験手法

X-RAY DIFFRACTION (2.05 Å)