8D3F

Crystal structure of human STAT1 in complex with the repeat region from Toxoplasma protein TgIST

8D3F の概要

• エントリーDOI: 10.2210/pdb8d3f/pdb
• 分子名称: Signal transducer and activator of transcription 1-alpha/beta,Inhibitor of STAT1-dependent transcription TgIST (1 entity in total)
• 機能のキーワード: signal transduction, transcriptional activation, pathogen effector, interferon signaling, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 73359.93

構造登録者

Huang, Z.,Liu, H.,Nix, J.C.,Amarasinghe, G.K.,Sibley, L.D. (登録日: 2022-06-01, 公開日: 2022-07-06, 最終更新日: 2023-10-25)

主引用文献

Huang, Z.,Liu, H.,Nix, J.,Xu, R.,Knoverek, C.R.,Bowman, G.R.,Amarasinghe, G.K.,Sibley, L.D.
The intrinsically disordered protein TgIST from Toxoplasma gondii inhibits STAT1 signaling by blocking cofactor recruitment.
Nat Commun, 13:4047-4047, 2022

PubMed Abstract: Signal transducer and activator of transcription (STAT) proteins communicate from cell-surface receptors to drive transcription of immune response genes. The parasite Toxoplasma gondii blocks STAT1-mediated gene expression by secreting the intrinsically disordered protein TgIST that traffics to the host nucleus, binds phosphorylated STAT1 dimers, and occupies nascent transcription sites that unexpectedly remain silenced. Here we define a core region within internal repeats of TgIST that is necessary and sufficient to block STAT1-mediated gene expression. Cellular, biochemical, mutational, and structural data demonstrate that the repeat region of TgIST adopts a helical conformation upon binding to STAT1 dimers. The binding interface is defined by a groove formed from two loops in the STAT1 SH2 domains that reorient during dimerization. TgIST binding to this newly exposed site at the STAT1 dimer interface alters its conformation and prevents the recruitment of co-transcriptional activators, thus defining the mechanism of blocked transcription.

PubMed: 35831295
DOI: 10.1038/s41467-022-31720-7

実験手法

X-RAY DIFFRACTION (2.97 Å)