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-Structure paper
タイトル | Activation of human STING by a molecular glue-like compound. |
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ジャーナル・号・ページ | Nat Chem Biol, Vol. 20, Issue 3, Page 365-372, Year 2024 |
掲載日 | 2023年10月12日 |
著者 | Jie Li / Stephen M Canham / Hua Wu / Martin Henault / Lihao Chen / Guoxun Liu / Yu Chen / Gary Yu / Howard R Miller / Viktor Hornak / Scott M Brittain / Gregory A Michaud / Antonin Tutter / Wendy Broom / Mary Ellen Digan / Sarah M McWhirter / Kelsey E Sivick / Helen T Pham / Christine H Chen / George S Tria / Jeffery M McKenna / Markus Schirle / Xiaohong Mao / Thomas B Nicholson / Yuan Wang / Jeremy L Jenkins / Rishi K Jain / John A Tallarico / Sejal J Patel / Lianxing Zheng / Nathan T Ross / Charles Y Cho / Xuewu Zhang / Xiao-Chen Bai / Yan Feng / |
PubMed 要旨 | Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its ...Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation of STING requires its high-order oligomerization, which could be induced by binding of the endogenous ligand, cGAMP, to the cytosolic ligand-binding domain. Here we report the discovery through functional screens of a class of compounds, named NVS-STGs, that activate human STING. Our cryo-EM structures show that NVS-STG2 induces the high-order oligomerization of human STING by binding to a pocket between the transmembrane domains of the neighboring STING dimers, effectively acting as a molecular glue. Our functional assays showed that NVS-STG2 could elicit potent STING-mediated immune responses in cells and antitumor activities in animal models. |
リンク | Nat Chem Biol / PubMed:37828400 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 4.0 Å |
構造データ | EMDB-29281, PDB-8flk: EMDB-29282, PDB-8flm: |
化合物 | ChemComp-1SY: ChemComp-Y6H: ChemComp-9IM: |
由来 |
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キーワード | IMMUNE SYSTEM / STING / innate immunity / molecular glue |