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 Wu, J, Sun, L, Chen, X, Du, F, Shi, H, Chen, C, Chen, ZJ	Science	2013
23258413	Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway Sun, L, Wu, J, Du, F, Chen, X, Chen, ZJ	Science	2013