National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35GM130289
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM143158
米国
Robert A. Welch Foundation
I-1702
米国
Robert A. Welch Foundation
I-1944
米国
引用
ジャーナル: Nat Chem Biol / 年: 2024 タイトル: Activation of human STING by a molecular glue-like compound. 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 / ...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 / 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.
名称: STING tetramer / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 詳細: STING tetramer, which can further assemblies into larger oligomers, induced by cGAMP and NVS-STG2
由来(天然)
生物種: Homo sapiens (ヒト)
分子量
理論値: 300 KDa
-
分子 #1: Stimulator of interferon genes protein
分子
名称: Stimulator of interferon genes protein / タイプ: protein_or_peptide / ID: 1 / コピー数: 4 / 光学異性体: LEVO