4KSY

Crystal structure of STING in complex with cGAMP

Summary for 4KSY

• Entry DOI: 10.2210/pdb4ksy/pdb
• Descriptor: Stimulator of interferon genes protein, cGAMP (3 entities in total)
• Functional Keywords: innate immunity, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 27855.06

Authors

Zhang, X.,Chen, Z.J.,Zhang, X.W. (deposition date: 2013-05-18, release date: 2013-06-12, Last modification date: 2024-02-28)

Primary citation

Zhang, X.,Shi, H.,Wu, J.,Zhang, X.,Sun, L.,Chen, C.,Chen, Z.J.
Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING.
Mol.Cell, 51:226-235, 2013

PubMed Abstract: The presence of microbial or self DNA in the cytoplasm of mammalian cells is a danger signal detected by the DNA sensor cyclic-GMP-AMP (cGAMP) synthase (cGAS), which catalyzes the production of cGAMP that in turn serves as a second messenger to activate innate immune responses. Here we show that endogenous cGAMP in mammalian cells contains two distinct phosphodiester linkages, one between 2'-OH of GMP and 5'-phosphate of AMP, and the other between 3'-OH of AMP and 5'-phosphate of GMP. This molecule, termed 2'3'-cGAMP, is unique in that it binds to the adaptor protein STING with a much greater affinity than cGAMP molecules containing other combinations of phosphodiester linkages. The crystal structure of STING bound to 2'3'-cGAMP revealed the structural basis of this high-affinity binding and a ligand-induced conformational change in STING that may underlie its activation.

PubMed: 23747010
DOI: 10.1016/j.molcel.2013.05.022

Experimental method

X-RAY DIFFRACTION (1.881 Å)