Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Parker Institute for Cancer Immunotherapy at Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Curr Opin Struct Biol. 2019 Dec;59:178-187. doi: 10.1016/j.sbi.2019.08.003. Epub 2019 Oct 6.
Cyclic GMP-AMP synthase (cGAS) is a signaling enzyme in human cells that controls immune-sensing of cytosolic DNA. The recent discoveries of diverse structural homologs of cGAS in animals and bacteria reveal that cGAS-like signaling is surprisingly ancient and widespread in biology. Together with the Vibrio cholerae protein dinucleotide cyclase in Vibrio (DncV), cGAS and DncV homologs comprise a family of cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes that synthesize noncanonical RNA signals including cyclic dinucleotides, cyclic trinucleotides, and linear oligonucleotides. Structural and biochemical breakthroughs provide a framework to understand how CD-NTase signaling allows cells to respond to changing environmental conditions. The CD-NTase family also includes uncharacterized human genes like MB21D2 and Mab21L1, highlighting emerging functions of cGAS-like signaling beyond innate immunity.
环鸟苷酸-腺苷酸合酶 (cGAS) 是人类细胞中的一种信号酶，它控制着细胞质 DNA 的免疫感应。最近在动物和细菌中发现了多种 cGAS 的结构同源物，这表明 cGAS 样信号在生物学中非常古老且广泛存在。与霍乱弧菌二核苷酸环化酶（DncV）一起，cGAS 和 DncV 同源物组成了 cGAS/DncV 样核苷酸转移酶（CD-NTase）酶家族，该酶家族合成非典型的 RNA 信号，包括环二核苷酸、环三核苷酸和线性寡核苷酸。结构和生化方面的突破为理解 CD-NTase 信号如何使细胞能够对环境变化做出反应提供了一个框架。CD-NTase 家族还包括未被表征的人类基因，如 MB21D2 和 Mab21L1，这突显了 cGAS 样信号在先天免疫之外的新兴功能。
