4kb6 | pdb_00004kb6

Structure of porcine cyclic GMP AMP synthase (CGAS) in complex with DNA, ATP and GTP

spinqualitylabelsall models 4kb6, resolution 3.08Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4kb6 is a 3 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, GTP, MG, ZN Related: 4jlx, 4jlz Gene: MB21D1 (Sus scrofa) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed 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. Structural mechanism of cytosolic DNA sensing by cGAS.,Civril F, Deimling T, de Oliveira Mann CC, Ablasser A, Moldt M, Witte G, Hornung V, Hopfner KP Nature. 2013 May 30. doi: 10.1038/nature12305. PMID:23722159 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cyclic GMP-AMP synthase

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