|Structure (2011) 19:418-29|
|Northeast Structural Genomics Consortium|
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IFI16 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.
|chemistry metabolism genetics |
|Crystallography, X-Ray DNA Nuclear Proteins Protein Interaction Domains and Motifs Escherichia coli Phosphoproteins DNA-Binding Proteins Binding Sites Interferons Transcriptional Activation Models, Molecular Recombinant Proteins Cell Line, Tumor Humans Crystallization Tumor Suppressor Protein p53 Protein Binding |
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