| Title | Rat and human STINGs profile similarly towards anticancer/antiviral compounds |
| Authors | Zhang, Heng Han, Min-Jie Tao, Jianli Ye, Zhao-Yang Du, Xiao-Xia Deng, Ming-Jing Zhang, Xiao-Yan Li, Lan-Fen Jiang, Zheng-Fan Su, Xiao-Dong |
| Affiliation | Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. Peking Univ, Sch Life Sci, Biodynam Opt Imaging Ctr BIOPIC, Beijing 100871, Peoples R China. |
| Keywords | CYCLIC-DI-GMP AGENT 5,6-DIMETHYLXANTHENONE-4-ACETIC ACID INNATE IMMUNITY CYTOSOLIC DNA AMP SYNTHASE ACTIVATION ADAPTER 2ND-MESSENGER DINUCLEOTIDE BINDING |
| Issue Date | 2015 |
| Publisher | SCIENTIFIC REPORTS |
| Citation | SCIENTIFIC REPORTS.2015,5. |
| Abstract | Cyclic dinucleotides (CDNs) and antitumor/antiviral agents (DMXAA and CMA) trigger STING-dependent innate immunity activation. Accumulative evidences have showed that DMXAA and CMA selectively activate mouse, but not human STING signaling. The mechanism underlying this species selectivity remains poorly understood. In this report, we have shown that human and rat STINGs display more similar signaling profiles toward DMXAA and CMA than that of human and mouse STINGs, suggesting that rat is more suitable for preclinical testing of STING-targeted drugs. We have also determined the crystal structures of both apo rat STING and its complex with cyclic GMP-AMP with 2'5' and 3'5' phosphodiester linkage (2'3'-cGAMP), a human endogenous CDN. Structure-guided biochemical analysis also revealed the functional importance of the connecting loop (A140-N152) between membrane and cytosolic domains in STING activation. Taken together, these findings reveal that rat STING is more closely related to human STING in terms of substrate preference, serving as a foundation for the development of STING-targeted drugs. |
| URI | http://hdl.handle.net/20.500.11897/435881 |
| ISSN | 2045-2322 |
| DOI | 10.1038/srep18035 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 生命科学学院 |
