8D3F

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

Summary for 8D3F

• Entry DOI: 10.2210/pdb8d3f/pdb
• Descriptor: Signal transducer and activator of transcription 1-alpha/beta,Inhibitor of STAT1-dependent transcription TgIST (1 entity in total)
• Functional Keywords: signal transduction, transcriptional activation, pathogen effector, interferon signaling, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 73359.93

Authors

Huang, Z.,Liu, H.,Nix, J.C.,Amarasinghe, G.K.,Sibley, L.D. (deposition date: 2022-06-01, release date: 2022-07-06, Last modification date: 2023-10-25)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.97 Å)