Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Rep. 2013 May 30;3(5):1362-8. doi: 10.1016/j.celrep.2013.05.008. Epub 2013 May 23.

Structure of human cGAS reveals a conserved family of second-messenger enzymes in innate immunity.

Author information

1
Department of Molecular & Cell Biology, Center for RNA Systems Biology, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.

Abstract

Innate immune recognition of foreign nucleic acids induces protective interferon responses. Detection of cytosolic DNA triggers downstream immune signaling through activation of cyclic GMP-AMP synthase (cGAS). We report here the crystal structure of human cGAS, revealing an unanticipated zinc-ribbon DNA-binding domain appended to a core enzymatic nucleotidyltransferase scaffold. The catalytic core of cGAS is structurally homologous to the RNA-sensing enzyme, 2'-5' oligo-adenylate synthase (OAS), and divergent C-terminal domains account for specific ligand-activation requirements of each enzyme. We show that the cGAS zinc ribbon is essential for STING-dependent induction of the interferon response and that conserved amino acids displayed within the intervening loops are required for efficient cytosolic DNA recognition. These results demonstrate that cGAS and OAS define a family of innate immunity sensors and that structural divergence from a core nucleotidyltransferase enables second-messenger responses to distinct foreign nucleic acids.

PMID:
23707061
PMCID:
PMC3800681
DOI:
10.1016/j.celrep.2013.05.008
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center