The N terminus of cGAS de‐oligomerizes the cGAS:DNA complex and lifts the DNA size restriction of core‐cGAS activity. Issue 6 (7th March 2017)

• Record Type: Journal Article
• Authors: Lee, Arum; Park, Eun‐Byeol; Lee, Janghyun; Choi, Byong‐Seok; Kang, Suk‐Jo
• Is Part Of: FEBS letters. Volume 591:Issue 6(2017)
• Page Start: 954
• Page End: 961
• Publication Date: 2017-03-07
• Subjects: cGAS -- innate immune system -- oligomerization; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.12598
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract :