Journal Article

DESY-2014-02579

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structural mechanism of cytosolic DNA sensing by cGAS

Civril, F. (Corresponding Author)Extern* ; Deimling, T.Extern* ; de Oliveira Mann, C. C.Extern* ; Ablasser, A. ; Moldt, M. ; Witte, G.Extern* ; Hornung, V. ; Hopfner, K.-P.Extern*

2013
Macmillan28177 London

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Please use a persistent id in citations: doi:10.1038/nature12305

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.

Note: (c) Macmillan Publishers Limited. Post referee fulltext in progress.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)
2. DOOR-User (DOOR)

Research Program(s):

1. PETRA Beamline P14 (POF2-54G14) (POF2-54G14)

Experiment(s):

1. PETRA Beamline P14 (PETRA III)

Appears in the scientific report 2013

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Database coverage:
; ; NCBI Molecular Biology Database ; SCOPUS

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