4LEV

Structure of human cGAS

Summary for 4LEV

• Entry DOI: 10.2210/pdb4lev/pdb
• Related: 4LEW 4LEy 4LEz
• Descriptor: Cyclic GMP-AMP synthase, ZINC ION (3 entities in total)
• Functional Keywords: ntase, dna sensor, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytosol: Q8N884
• Total number of polymer chains: 2
• Total formula weight: 86897.19

Authors

Li, P. (deposition date: 2013-06-26, release date: 2013-12-25, Last modification date: 2024-10-16)

Primary citation

Li, X.,Shu, C.,Yi, G.,Chaton, C.T.,Shelton, C.L.,Diao, J.,Zuo, X.,Kao, C.C.,Herr, A.B.,Li, P.
Cyclic GMP-AMP Synthase Is Activated by Double-Stranded DNA-Induced Oligomerization.
Immunity, 39:1019-1031, 2013

PubMed Abstract: Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor mediating innate antimicrobial immunity. It catalyzes the synthesis of a noncanonical cyclic dinucleotide, 2',5' cGAMP, that binds to STING and mediates the activation of TBK1 and IRF-3. Activated IRF-3 translocates to the nucleus and initiates the transcription of the IFN-β gene. The structure of mouse cGAS bound to an 18 bp dsDNA revealed that cGAS interacts with dsDNA through two binding sites, forming a 2:2 complex. Enzyme assays and IFN-β reporter assays of cGAS mutants demonstrated that interactions at both DNA binding sites are essential for cGAS activation. Mutagenesis and DNA binding studies showed that the two sites bind dsDNA cooperatively and that site B plays a critical role in DNA binding. The structure of mouse cGAS bound to dsDNA and 2',5' cGAMP provided insight into the catalytic mechanism of cGAS. These results demonstrated that cGAS is activated by dsDNA-induced oligomerization.

PubMed: 24332030
DOI: 10.1016/j.immuni.2013.10.019

Experimental method

X-RAY DIFFRACTION (1.952 Å)