AI Article Synopsis
- The binding of DNA to cGAS initiates the production of cGAMP, which triggers the body's innate immune responses.
- The presence of the disordered and positively charged cGAS N terminus increases the efficiency of cGAS-DNA interactions, leading to the formation of liquid-like droplets that activate cGAS.
- Long DNA molecules are more effective in enhancing cGAS activity compared to shorter ones, and free zinc ions further boost cGAS function by aiding in the DNA-cGAS phase separation.
Article Abstract
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. The disordered and positively charged cGAS N terminus enhanced cGAS-DNA phase separation by increasing the valencies of DNA binding. Long DNA was more efficient in promoting cGAS liquid phase separation and cGAS enzyme activity than short DNA. Moreover, free zinc ions enhanced cGAS enzyme activity both in vitro and in cells by promoting cGAS-DNA phase separation. These results demonstrated that the DNA-induced phase transition of cGAS promotes cGAMP production and innate immune signaling.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9417938 | PMC |
| http://dx.doi.org/10.1126/science.aat1022 | DOI Listing |
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