Eukaryotic ADCY7 catalyzes the production of c-di-AMP to activate the NLRP3 inflammasome

• Published in: Nature chemical biology Vol. 21; no. 8; pp. 1283 - 1291
• Main Authors: Liu, Qiannv, Tang, Zhiheng, Qian, Yan, Wang, Chunlei, Kong, Chun, Li, Mengqian, Geng, Xiangyang, Zhang, Yan, Cheng, Xiangyun, Ren, Chao, Wang, Kai, Bai, Lin, Wang, Lin, Jiang, Dong, Wang, Shuo, Liu, Xiaoyun, Xia, Pengyan
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2025; Nature Publishing Group
• Subjects: 631/250/249; 631/250/255; Adenosine monophosphate; Adenosine triphosphate; Adenylate cyclase; Adenylyl Cyclases - deficiency; Adenylyl Cyclases - genetics; Adenylyl Cyclases - metabolism; Agonists; Animals; Binding; Biochemical Engineering; Biochemistry; Bioorganic Chemistry; Catalysis; Cell Biology; Cell culture; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Clonal deletion; Cyclic AMP; Cytotoxicity; Dimers; Dinucleoside Phosphates - metabolism; Enzymatic activity; Gene deletion; Genes; HEK293 Cells; Humans; Inflammasomes; Inflammasomes - metabolism; Leucine; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondrial DNA; Mortality; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Nucleotides; Physiology; Potassium; Proteins; TLR9 protein; Toll-Like Receptor 9 - agonists; Toll-Like Receptor 9 - metabolism; Toll-like receptors

Toll-like receptor 9 (TLR9) agonists cause activation of nucleotide-binding domain, leucine-rich repeat protein 3 (NLRP3) inflammasomes but the mechanism is not clear. We found that there is a second signal downstream of TLR9 that induces NLRP3 inflammasome activation. Through screening, adenylate c...