环状GMP-AMP合酶识别DNA的物理特征
Cyclic GMP-AMP synthase recognizes the physical features of DNA
影响因子:8.40000
分区:医学2区 / 药学1区 化学：综合2区
发表日期:2025 Feb
作者:
Ling Dong, Yue-Ru Hou, Na Xu, Xiao-Qian Gao, Zhen Sun, Qing-Kai Yang, Li-Na Wang
摘要
环状GMP-AMP合酶（CGA）是一种主要的胞质DNA传感器，在先天免疫中起重要作用。在与双链DNA（DSDNA）结合后，CGAS利用GTP和ATP合成第二个Messenger Cyclic Cyclic GMP-AMP（CGAMP）。然后，CGAMP与内质网中干扰素基因（STING）的衔接蛋白刺激剂结合，从而导致转录因子干扰素调节因子3（IRF3）的激活以及随后的I型干扰素诱导。一个重要的问题是CGA如何区分自我和非自我DNA。尽管CGA在没有歧视的情况下与DNA的磷酸骨架结合，但其激活受到物理特征的影响，例如DNA长度，DNA间距离和机械柔韧性。这表明CGA对DNA的识别可能取决于这些物理特征。在本文中，我们总结了有关抗病毒防御，细胞衰老和抗肿瘤反应的CGAS丁字道途径研究的最新进展，并专注于基于物理特征的DNA识别机制。
Abstract
Cyclic GMP-AMP synthase (cGAS) is a major cytosolic DNA sensor that plays a significant role in innate immunity. Upon binding to double stranded DNA (dsDNA), cGAS utilizes GTP and ATP to synthesize the second messenger cyclic GMP-AMP (cGAMP). The cGAMP then binds to the adapter protein stimulator of interferon genes (STING) in the endoplasmic reticulum, resulting in the activation of the transcription factor interferon regulatory factor 3 (IRF3) and subsequent induction of type I interferon. An important question is how cGAS distinguishes between self and non-self DNA. While cGAS binds to the phosphate backbone of DNA without discrimination, its activation is influenced by physical features such as DNA length, inter-DNA distance, and mechanical flexibility. This suggests that the recognition of DNA by cGAS may depend on these physical features. In this article we summarize the recent progress in research on cGAS-STING pathway involved in antiviral defense, cellular senescence and anti-tumor response, and focus on DNA recognition mechanisms based on the physical features.