The detection of pathogens through nucleic acid sensors is a defining principle of innate immunity. RNA-sensing and DNA-sensing receptors sample subcellular compartments for foreign nucleic acids and, upon recognition, trigger immune signalling pathways
The aforementioned data suggest that the binding site of XQ2 may locate at the DNA binding site of cGAS. We tried to get the cocrystal structure of cGAS in complex with XQ2 to characterize the detailed binding mode of XQ2 on cGAS, but no complex structure was obtained. We thus carried out...
cGAS-STING通路是先天免疫系统中识别胞质DNA的重要机制,能够快速检测标志病原体入侵的胞质DNA并触发抗感染免疫反应。然而,当细胞受到损伤时,积累的自身DNA也可能异常激活cGAS,启动免疫反应。过度激活cGAS-STING通路可能引发严重的自身免疫性疾病。本文回顾了...
These cyclopeptides specifically bind to the DNA binding site of cGAS and block the binding of dsDNA with cGAS, subsequently inhibit dsDNA-induced liquid phase condensation and activation of cGAS. The specificity and potency of one optimal lead XQ2B were characterized in cellular assays. Concordantly...
The binding of DNA to cyclic GMP-AMP synthase (cGAS) leads to the production of the secondary messenger cyclic GMP-AMP (cGAMP), which activates innate immune responses. Here, we show that DNA binding to cGAS robustly induced the formation of liquidlike droplets in which cGAS was activated. ...
G3BP1 enhanced DNA binding of cGAS by promoting the formation of large cGAS complexes. G3BP1 deficiency led to inefficient DNA binding by cGAS and inhibited cGAS-dependent interferon (IFN) production. The G3BP1 inhibitor epigallocatechin gallate (EGCG) disrupted existing G3BP1-cGAS complexes and ...
Cytosolic DNA sensing, the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is an important novel role in the immune system. Multiple STING agonists were developed for cancer therapy study with great results achieved in pre-clinical work. Recent progress in the mechanica...
Intracellular DNA-sensing pathway cGAS-STING, inflammasomes and pyroptosis act as critical natural immune signaling axes for microbial infection, chronic inflammation, cancer progression and organ degeneration, but the mechanism and regulation of the cro
is vital for DNA binding, enzymatic activity, and downstream innate-immune signaling activation. Notably, the cGAS C-terminal domain contains a strong DNA-binding site A, a weaker DNA-binding site B,31,48and an additional DNA-binding site C49that facilitates cGAS activation and phase transition...
cGAS primarily engages the nucleosome core particle (NCP) through binding to the so-called acidic patch composed of Glu61, Asp90, Glu92, which are interacted with Arg236, Lys254, Arg255 in DNA binding B-site via electrostatic interaction [41]. Substitutions of either arginine residues on cGAS...