A virus-induced conformational switch of STAT1-STAT2 dimers boosts antiviral defenses

• 作 者: Yuxin Wang Qiaoling Song Wei Huang Yuxi Lin Xin Wang Chenyao Wang Belinda Willard Chenyang Zhao Jing Nan Elise Holvey-Bates Zhuoya Wang Derek Taylor Jinbo Yang George R.Stark
• 机 构: Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland,
• 出 处: 细胞研究（英文版）
• 发表日期: 2021年2期

Type I interferons(IFN-I)protect us from viral infections.Signal transducer and activator of transcription 2(STAT2)is a key component of interferon-stimulated gene factor 3(ISGF3),which drives gene expression in response to IFN-I.Using electron microscopy,we found that,in naive cells,U-STAT2,lacking the activating tyrosine phosphorylation,forms a heterodimer with U-STAT1 in an inactive,anti-parallel conformation.A novel phosphorylation of STAT2 on T404 promotes IFN-I signaling by disrupting the U-STAT1-U-STAT2 dimer,facilitating the tyrosine phosphorylation of STATs 1 and 2 and enhancing the DNA-binding ability of ISGF3.IKK-e,activated by virus infection,phosphorylates T404 directly.Mice with a T-A mutation at the corresponding residue(T403)are highly susceptible to virus infections.We conclude that T404 phosphorylation drives a critical conformational switch that,by boosting the response to IFN-I in infected cells,enables a swift and efficient antiviral defense.