Structural mechanism of cytosolic DNA sensing by cGAS

Filiz Civril, Tobias Deimling, Carina C. de Oliveira Mann, Andrea Ablasser, Manuela Moldt, Gregor Witte, Veit Hornung and Karl-Peter Hopfner ()
Additional contact information
Filiz Civril: Ludwig-Maximilians-University, 81377 Munich, Germany
Tobias Deimling: Ludwig-Maximilians-University, 81377 Munich, Germany
Carina C. de Oliveira Mann: Ludwig-Maximilians-University, 81377 Munich, Germany
Andrea Ablasser: Institute for Clinical Chemistry & Clinical Pharmacology, Unit for Clinical Biochemistry, University Hospital, University of Bonn, 53127 Bonn, Germany
Manuela Moldt: Ludwig-Maximilians-University, 81377 Munich, Germany
Gregor Witte: Ludwig-Maximilians-University, 81377 Munich, Germany
Veit Hornung: Institute for Clinical Chemistry & Clinical Pharmacology, Unit for Clinical Biochemistry, University Hospital, University of Bonn, 53127 Bonn, Germany
Karl-Peter Hopfner: Ludwig-Maximilians-University, 81377 Munich, Germany

Nature, 2013, vol. 498, issue 7454, 332-337

Abstract: Abstract Cytosolic DNA arising from intracellular bacterial or viral infections is a powerful pathogen-associated molecular pattern (PAMP) that leads to innate immune host defence by the production of type I interferon and inflammatory cytokines. Recognition of cytosolic DNA by the recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production of cGAMP to activate the stimulator of interferon genes (STING). Here we report the crystal structure of cGAS alone and in complex with DNA, ATP and GTP along with functional studies. Our results explain the broad DNA sensing specificity of cGAS, show how cGAS catalyses dinucleotide formation and indicate activation by a DNA-induced structural switch. cGAS possesses a remarkable structural similarity to the antiviral cytosolic double-stranded RNA sensor 2′-5′oligoadenylate synthase (OAS1), but contains a unique zinc thumb that recognizes B-form double-stranded DNA. Our results mechanistically unify dsRNA and dsDNA innate immune sensing by OAS1 and cGAS nucleotidyl transferases.

Date: 2013
References: Add references at CitEc
Citations: View citations in EconPapers (7)

Downloads: (external link)
https://www.nature.com/articles/nature12305 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:498:y:2013:i:7454:d:10.1038_nature12305

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature12305

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().