4JLX: Structure of Porcine Cyclic Gmp-amp Synthase (Cgas)

Citation:
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.
PDB ID: 4JLXDownload
MMDB ID: 110912
PDB Deposition Date: 2013/3/13
Updated in MMDB: 07/2013 
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit: monomeric; determined by author, and by software (PISA)
Molecular Components
Label Count Molecule
Protein (1 molecule)
1
Uncharacterized Protein
Molecule annotation
Chemicals (7 molecules)
1
1
2
3
3
1
4
2
* Click molecule labels to explore molecular sequence information.

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