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The N terminus of cGAS de‐oligomerizes the cGAS : DNA complex and lifts the DNA size restriction of core‐ cGAS activity
Author(s) -
Lee Arum,
Park EunByeol,
Lee Janghyun,
Choi ByongSeok,
Kang SukJo
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12598
Subject(s) - dna , chemistry , microbiology and biotechnology , c terminus , n terminus , biochemistry , biology , gene , peptide sequence , amino acid
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.