Reactome | STING binds cyclic GMP-AMP

STING binds cyclic GMP-AMP

Stable Identifier

R-HSA-3244643

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane, cytosol, cytoplasmic vesicle membrane

ReviewStatus

5/5

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Direct binding assays with radiolabeled substrate showed that the association of STING protein (residues 139-379) with [32P]-cGAMP was inhibited in the presence of competing cold cGAMP, c-di-GMP or c-di-AMP, suggesting that the cGAMP binding sites on STING might overlap with those that interact with c-di-GMP and c-di-AMP (Wu J et al.2013). Indeed, mutations of several residues that were shown to participate in the binding of STING to c-di-GMP, including S161Y, Y240S and N242A, also impaired the binding of STING to cGAMP (Yin Q et al. 2012; Wu J et al.2013). Structural study revealed that cGAMP generated by cGAS contains G(2',5')pA and A(3',5')pG phosphodiester linkages, which is distinct from bacterial 3',5' cyclic dinucleotides (Gao P et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
23258412	Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA Chen, C, Chen, ZJ, Du, F, Sun, L, Wu, J, Shi, H, Chen, X	Science	2013
23258413	Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway Chen, ZJ, Du, F, Wu, J, Sun, L, Chen, X	Science	2013