Structural highlights
5cfm is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| Related: | 5cfl, 5cfn, 5cfo, 5cfp, 5cfq, 5cfr |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Publication Abstract from PubMed
In humans, the cGAS-STING immunity pathway signals in response to cytosolic DNA via 2',3' cGAMP, a cyclic dinucleotide (CDN) second messenger containing mixed 2'-5' and 3'-5' phosphodiester bonds. Prokaryotes also produce CDNs, but these are exclusively 3' linked, and thus the evolutionary origins of human 2',3' cGAMP signaling are unknown. Here we illuminate the ancient origins of human cGAMP signaling by discovery of a functional cGAS-STING pathway in Nematostella vectensis, an anemone species >500 million years diverged from humans. Anemone cGAS appears to produce a 3',3' CDN that anemone STING recognizes through nucleobase-specific contacts not observed in human STING. Nevertheless, anemone STING binds mixed-linkage 2',3' cGAMP indistinguishably from human STING, trapping a unique structural conformation not induced by 3',3' CDNs. These results reveal that human mixed-linkage cGAMP achieves universal signaling by exploiting a deeply conserved STING conformational intermediate, providing critical insight for therapeutic targeting of the STING pathway.
Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2',3' cGAMP Signaling.,Kranzusch PJ, Wilson SC, Lee AS, Berger JM, Doudna JA, Vance RE Mol Cell. 2015 Aug 19. pii: S1097-2765(15)00580-8. doi:, 10.1016/j.molcel.2015.07.022. PMID:26300263[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kranzusch PJ, Wilson SC, Lee AS, Berger JM, Doudna JA, Vance RE. Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2',3' cGAMP Signaling. Mol Cell. 2015 Aug 19. pii: S1097-2765(15)00580-8. doi:, 10.1016/j.molcel.2015.07.022. PMID:26300263 doi:http://dx.doi.org/10.1016/j.molcel.2015.07.022
