| First Author | Lee A | Year | 2017 |
| Journal | FEBS Lett | Volume | 591 |
| Issue | 6 | Pages | 954-961 |
| PubMed ID | 28214358 | Mgi Jnum | J:241014 |
| Mgi Id | MGI:5897502 | Doi | 10.1002/1873-3468.12598 |
| Citation | Lee A, et al. (2017) The N terminus of cGAS de-oligomerizes the cGAS:DNA complex and lifts the DNA size restriction of core-cGAS activity. FEBS Lett 591(6):954-961 |
| abstractText | Cyclic GMP-AMP synthase (cGAS) is a DNA-sensing enzyme in the innate immune system. Recent studies using core-cGAS lacking the N terminus investigated the mechanism for binding of double-stranded (ds) DNA and synthesis of 2',3'-cyclic GMP-AMP (cGAMP), a secondary messenger that ultimately induces type I interferons. However, the function of the N terminus of cGAS remains largely unknown. Here, we found that the N terminus enhanced the activity of core-cGAS in vivo. Importantly, the catalytic activity of core-cGAS decreased as the length of double-stranded DNA (dsDNA) increased, but the diminished activity was restored by addition of the N terminus. Furthermore, the N terminus de-oligomerized the 2 : 2 complex of core-cGAS and dsDNA into a 1 : 1 complex, suggesting that the N terminus enhanced the activity of core-cGAS by facilitating formation of a monomeric complex of cGAS and DNA. |
