title: The N terminus of cGAS de-oligomerizes the cGAS:DNA complex and lifts the DNA size restriction of core-cGAS activity.
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 : 1 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.
authors.affiliation: Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Arum
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Eun-Byeol
authors.initials: EB
authors.lastname: Park
authors.affiliation: Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Janghyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Byong-Seok
authors.initials: BS
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Suk-Jo
authors.initials: SJ
authors.lastname: Kang
mesh_terms: D000818:Animals; D055162:Biocatalysis; D002151:Calorimetry / Q000379:methods; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D046911:Macromolecular Substances / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009712:Nucleotides, Cyclic / Q000096:biosynthesis; D009713:Nucleotidyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D004247:DNA; D046911:Macromolecular Substances; D009712:Nucleotides, Cyclic; D009713:Nucleotidyltransferases; C584311:cyclic guanosine monophosphate-adenosine monophosphate; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
keywords: 
  cGAS
  ; innate immune system; oligomerization