DNA-Bound p53-DNA-Binding Domain Interconverts between Multiple Conformations: Implications for Partner Protein Recognition

Protein-protein interaction networks are critical components of cellular regulation. Hub proteins, defined by their ability to interact with numerous protein partners, are the pivots of these networks. A hypothesis that an ensemble of rapidly interconverting conformational states contributes significantly to the ability of hub proteins to interact with diverse partners has been proposed. The master gene regulator p53 is a prototype multidomain hub protein. Its DNA-binding domain alone is involved in interactions with many of its partner proteins. We investigated the dynamics of the p53 DNA-binding domain by N-15-NMR Carr-Purcell-Meiboom-Gill relaxation methods. In the DNA-bound state, we detected conformational exchanges in the domain in the microsecond to millisecond timescale, while dynamics at this timescale was not detectable in the free state. This suggests that the binding of p53 to specific DNA sequences promotes exchange between two or more conformational states, creating a broad conformational repertoire necessary for interacting with many partner proteins.

Automated summary

Protein-protein interaction networks rely on hub proteins that can interact with numerous partners, with the ability possibly influenced by rapid conformational state changes. The master gene regulator p53, as a prototype multidomain hub protein, demonstrates conformational exchanges in its DNA-binding domain when interacting with various partner proteins, suggesting a broad conformational repertoire facilitated by binding to specific DNA sequences.