Proximal proteins of the type I interferon signaling cascade

Deciphering the intricate dynamic events governing type I interferon (IFN) signaling is critical to unravel key regulatory mechanisms in host antiviral defense. Here, we leveraged TurboID-based proximity labeling coupled with affinity purification-mass spectrometry to comprehensively map temporal changes to the proximal human proteomes of all seven canonical type I IFN signaling cascade members following IFN stimulation. This established a network of 108 proteins in close proximity to the core members IFNAR1, IFNAR2, JAK1, TYK2, STAT1, STAT2, and IRF9, and validated several known protein assemblies, while also revealing novel, transient associations between key signaling molecules.