4O6A: Mouse Cyclic Gmp-amp Synthase (cgas) In Complex With Dna

Citation:
Abstract
The presence of DNA in the cytoplasm is a danger signal that triggers immune and inflammatory responses. Cytosolic DNA binds to and activates cyclic GMP-AMP (cGAMP) synthase (cGAS), which produces the second messenger cGAMP. cGAMP binds to the adaptor protein STING and activates a signaling cascade that leads to the production of type I interferons and other cytokines. Here, we report the crystal structures of human cGAS in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms. These structures reveal switch-like conformational changes of an activation loop that result in the rearrangement of the catalytic site. The structure of DNA-bound cGAS reveals a complex composed of dimeric cGAS bound to two molecules of DNA. Functional analyses of cGAS mutants demonstrate that both the protein-protein interface and the two DNA binding surfaces are critical for cGAS activation. These results provide insights into the mechanism of DNA sensing by cGAS.
PDB ID: 4O6ADownload
MMDB ID: 117332
PDB Deposition Date: 2013/12/20
Updated in MMDB: 2014/03
Experimental Method:
x-ray diffraction
Resolution: 1.86  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4O6A: hexameric; determined by author and by software (PISA)
Molecular Components in 4O6A
Label Count Molecule
Proteins (2 molecules)
2
Cyclic Gmp-amp Synthase(Gene symbol: Mb21d1)
Molecule annotation
Nucleotides(2 molecules)
2
Dna1
Molecule annotation
2
Dna2
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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