Intrinsically disordered pathogen effector alters the STAT1 dimer to prevent recruitment of co-transcriptional activators CBP/p300
Huang, Z.; Liu, H.; Nix, J.; Knoverek, C. R.; Bowman, G. R.; Amarasinghe, G. K.; Sibley, L. D.
Show abstract
Signal transducer and activator of transcription (STATs) proteins signal 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 unexpectantly remain silenced. Here we define a core repeat region within internal repeats of TgIST that is necessary and sufficient to block STAT1-mediated gene expression. Cellular, biochemical, mutational, and structural studies 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 altered its conformation and prevented recruitment of co-transcriptional activators, thus defining the mechanism of blocked transcription.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Structure of the TELO2-TTI1-TTI2 complex and its function in TOR recruitment to the R2TP chaperone 94%
- ATAC and SAGA coactivator complexes utilize co-translational assembly, but their cellular localization properties and functions are distinct 94%
- ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes 94%
Similar papers in this journal
- Structure and mechanism of the human CTDNEP1-NEP1R1 membrane protein phosphatase complex necessary to maintain ER membrane morphology 95%
- Hybrid histidine kinase activation by cyclic di-GMP- mediated domain liberation 94%
- Structural basis for coupling of the WASH subunit FAM21 with the endosomal SNX27-Retromer complex 94%
Similar papers in this journal
- Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility 94%
- Phage lysis protein LysM acts as a wedge to block MurJ conformational changes 94%
- Structural basis for assembly of TRAPPII complex and specific activation of GTPase Ypt31/32 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.