2018年8月17日 · 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. We have shown that DNA binding to cGAS robustly induced the formation of liquidlike droplets in which cGAS was activated.

2024年9月25日 · By establishing a genetic code expansion orthogonal system for lactyl-lysine incorporation, we demonstrate that the presence of a lactyl moiety at a specific cGAS amino-terminal site abolishes...

2022年2月11日 · Biomolecular condensates are widely observed to directly regulate key cellular processes involved in cancer cell pathology, and the dysregulation of LLPS is increasingly implicated as a...

2018年7月5日 · Du and Chen show that DNA binding to its cytoplasmic sensor, cyclic GMP–AMP synthase (cGAS), results in liquid droplets containing activated cGAS (see the Perspective by Ablasser). This phenomenon occurs through multivalent interactions, augmented by zinc, between DNA binding domains on cGAS and DNA in a length-dependent manner.

2022年7月8日 · DNA-induced LLPS of cGAS, driven by multivalent interactions between cGAS and DNA, is essential in vivo to induce cGAS activation and to trigger the cGAS–STING signaling pathway (30, 38). On the other hand, mutation and truncation of cGAS and short DNA (< 45 bp) attenuate the oligomerization and LLPS of cGAS–DNA, resulting in reduced or ...

2021年10月21日 · cGAS LLPS depends not only on the concentration of dsDNA but also its length, with longer dsDNA providing more binding sites and thus greater multivalency. In addition to DNA binding, cGAS catalytic activity requires Zn 2+ , which stabilizes the binding of cGAS to B-form DNA and activates its nucleotidyltransferase (NTase) activity ( Civril et ...

2025年1月26日 · cGAS （环磷酸鸟苷-腺苷合酶） 是一种关键的胞质DNA传感器，能够识别细胞质中的双链DNA （dsDNA） ，并催化ATP和GTP合成环状小分子cGAMP 【1, 2】。 cGAMP作为第二信使，与STING结合，激活下游的I型干扰素和其他免疫调节基因的表达，从而引发免疫应答。 cGAS参与了机体的免疫防御、慢性炎症以及抗肿瘤等过程 【3】。 cGAS包含两个结构域：N端无序区 （IDR） -cGASNterm和催化结构域 （cGASCD） 。 cGAS催化结构域 （cGASCD） …

2024年6月25日 · Cyclic GMP-AMP synthase (cGAS) undergoes liquid-liquid phase separation (LLPS) to trigger downstream signaling upon double-stranded DNA (dsDNA) stimulation, and the condensed cGAS colocalizes with stress granules (SGs).

进而得出结论，保护 dna免受trex1降解可能是cgas llps促进dna感知的主要模式。研究人员通过免疫亲和纯化技术和免疫荧光染色实验发现，除dna外，多种rna结合蛋白虽然不能诱导cgas产生cgamp，但也可与cgas发生llps ，来微调cgas的活性。

2022年7月8日 · Cyclic GMP-AMP synthase (cGAS), as a DNA sensor, plays an important role in cGAS-STING pathway, which further induces expression of type I interferon as the innate immune response. Previous studies reported that liquid-liquid phase separation (LLPS) driven by cGAS and long DNA is essential to promot …