5CFL

Crystal structure of anemone STING (Nematostella vectensis) in complex with 3', 3' c-di-GMP, c[G(3', 5')pG(3', 5')p]

5CFL の概要

• エントリーDOI: 10.2210/pdb5cfl/pdb
• 関連するPDBエントリー: 5CFM 5CFN 5CFO 5CFP 5CFQ 5CFR
• 分子名称: Stimulator of Interferon Genes, 9,9'-[(2R,3R,3aS,5S,7aR,9R,10R,10aS,12S,14aR)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecine-2,9-diyl]bis(2-amino-1,9-dihydro-6H-purin-6-one), CITRATE ANION, ... (4 entities in total)
• 機能のキーワード: sting, cyclic-dinucleotide binding domain, immune system
• 由来する生物種: Nematostella vectensis (Starlet sea anemone)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44898.26

構造登録者

Kranzusch, P.J.,Wilson, S.C.,Lee, A.S.Y.,Berger, J.M.,Doudna, J.A.,Vance, R.E. (登録日: 2015-07-08, 公開日: 2015-08-26, 最終更新日: 2024-03-06)

主引用文献

Kranzusch, P.J.,Wilson, S.C.,Lee, A.S.,Berger, J.M.,Doudna, J.A.,Vance, R.E.
Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2',3' cGAMP Signaling.
Mol.Cell, 59:891-903, 2015

PubMed Abstract: 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.

PubMed: 26300263
DOI: 10.1016/j.molcel.2015.07.022

実験手法

X-RAY DIFFRACTION (1.836 Å)