袁俊杰 文献简报21.9.24(2022年-2023年).pdfVIP

袁俊杰 文献简报 2021-09-26 Systematicprofiling ofprotein complex dynamics revealsDNA-PK phosphorylation ofIFI16 en route to herpesvirusimmunity JoshuaL.Justice,MichelleA.Kennedy et al. Science DOI:10.1126/sciadv.abg6680 ABSTRACT: Dynamically shifting protein-protein interactions (PPIs) regulate cellular responses to viruses and the resulting immune signaling. Here, we use thermal proximity coaggregation (TPCA) mass spectrometry to characterize the on-off behavior of PPIs during infection with herpes simplex virus 1 (HSV-1), a virus with an ancient history of coevolution with hosts. Advancing the TPCA analysis to infer associations de novo, we build a time-resolved portrait of thousands of host-host, virus-host, and virus-virus PPIs. We demonstrate that, early in infection, the DNA sensor IFI16 recruits the active DNA damage response kinase, DNA-dependent protein kinase (DNA-PK),to incomingviral DNA at the nuclear periphery. We establish IFI16 T149 as a substrate of DNA-PK upon viral infection or DNA damage. This phosphorylation promotes IFI16-driven cytokine responses. Together, we characterize the global dynamics of PPIs during HSV-1 infection, uncovering the co-regulation 袁俊杰 文献简报 2021-09-26 of IFI16 and DNA-PK functions as a missing link in immunity to herpesvirusinfection. 动态变化的蛋白质 蛋白质相互作用- (PPI) 调节细胞对病毒的反 应和由此产生的免疫信号。在这里，我们使用热邻近共聚集 (TPCA) 质谱法来表征 PPI 在感染单纯疱疹病毒 1(HSV-1) 期间的开关行为， 这种病毒与宿主有着古老的共同进化历史。推进 TPCA 分析以从头 推断关联，我们构建了数千个宿主宿主、病毒宿主和病毒病毒- - - PPI 的时间分辨画像。我们证明，在感染早期，DNA 传感器 IFI16 将活 性 DNA 损伤反应激酶、DNA 依赖性蛋白激酶 (DNA-PK) 招募到 核外围传入的病毒 DNA。我们建立 IFI16 T149 作为病毒感染或 DNA 损伤后 DNA-PK 的底物。这种磷酸化促进了 IFI16 驱动的细 胞因子反应。 袁俊杰 文献简报