5UXF

Crystal Structure of mouse RECON (AKR1C13) in complex with Cyclic di-AMP

5UXF の概要

• エントリーDOI: 10.2210/pdb5uxf/pdb
• 分子名称: Dihydrodiol dehydrogenase, (2R,3R,3aS,5R,7aR,9R,10R,10aS,12R,14aR)-2,9-bis(6-amino-9H-purin-9-yl)octahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8 ]tetraoxadiphosphacyclododecine-3,5,10,12-tetrol 5,12-dioxide (3 entities in total)
• 機能のキーワード: cyclic di-amp, aldo-keto reductase, tim barrel, oxidoreductase
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39949.44

構造登録者

Luo, S.,Tong, L. (登録日: 2017-02-22, 公開日: 2017-04-19, 最終更新日: 2024-03-06)

主引用文献

McFarland, A.P.,Luo, S.,Ahmed-Qadri, F.,Zuck, M.,Thayer, E.F.,Goo, Y.A.,Hybiske, K.,Tong, L.,Woodward, J.J.
Sensing of Bacterial Cyclic Dinucleotides by the Oxidoreductase RECON Promotes NF-kappa B Activation and Shapes a Proinflammatory Antibacterial State.
Immunity, 46:433-445, 2017

PubMed Abstract: Bacterial and host cyclic dinucleotides (cdNs) mediate cytosolic immune responses through the STING signaling pathway, although evidence suggests that alternative pathways exist. We used cdN-conjugated beads to biochemically isolate host receptors for bacterial cdNs, and we identified the oxidoreductase RECON. High-affinity cdN binding inhibited RECON enzyme activity by simultaneously blocking the substrate and cosubstrate sites, as revealed by structural analyses. During bacterial infection of macrophages, RECON antagonized STING activation by acting as a molecular sink for cdNs. Bacterial infection of hepatocytes, which do not express STING, revealed that RECON negatively regulates NF-κB activation. Loss of RECON activity, via genetic ablation or inhibition by cdNs, increased NF-κB activation and reduced bacterial survival, suggesting that cdN inhibition of RECON promotes a proinflammatory, antibacterial state that is distinct from the antiviral state associated with STING activation. Thus, RECON functions as a cytosolic sensor for bacterial cdNs, shaping inflammatory gene activation via its effects on STING and NF-κB.

PubMed: 28329705
DOI: 10.1016/j.immuni.2017.02.014

実験手法

X-RAY DIFFRACTION (1.501 Å)