Interferon-Inducible Protein 16: Insight into the Interaction with Tumor Suppressor p53

SummaryIFI16 is a member of the interferon-inducible HIN-200 family of nuclear proteins. It has been implicated in transcriptional regulation by modulating protein-protein interactions with p53 tumor suppressor protein and other transcription factors. However, the mechanisms of interaction remain unknown. Here, we report the crystal structures of both HIN-A and HIN-B domains of IFI16 determined at 2.0 and 2.35 Å resolution, respectively. Each HIN domain comprises a pair of tightly packed OB-fold subdomains that appear to act as a single unit. We show that both HIN domains of IFI16 are capable of enhancing p53-DNA complex formation and transcriptional activation via distinctive means. HIN-A domain binds to the basic C terminus of p53, whereas the HIN-B domain binds to the core DNA-binding region of p53. Both interactions are compatible with the DNA-bound state of p53 and together contribute to the effect of full-length IFI16 on p53-DNA complex formation and transcriptional activation.

► Structures of a HIN domain revealing a pair of tandem OB folds in a rigid orientation relative to one another
► Structures reveal functional differences between the two homologous HIN domains of IFI16
► Enhancement of p53 DNA binding and transactivation by both HIN domains of IFI16
► SAXS reveals a shape of full-length IFI16 consistent with potential function as a scaffold protein