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Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING

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Zhang, Xu, Shi, Heping, Wu, Jiaxi, Zhang, Xuewu, Sun, Lijun, Chen, Chuo, Chen, Zhijian J.·2013·Molecular Cell

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.

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Metadata

Authors
Zhang, X., Shi, H., Wu, J., Zhang, X., Sun, L., Chen, C., & Chen, Z. J.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2013-07
Volume
51
Issue
2
Pages
226-235
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2066818317
Cited by
1,071
References
5
FWCI
24.07
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING. https://app.cochat.ai/papers/10.1016/j.molcel.2013.05.022
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Zhang, X., Shi, H., Wu, J., Zhang, X., Sun, L., Chen, C., & Chen, Z. J. (2013). Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING. Molecular Cell. https://doi.org/10.1016/j.molcel.2013.05.022

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