P53 is an important tumor suppressor referred to as guardian of the genome. It is also implicated in ageing and has the potential to arrest the cell cycle.

To exert its effect p53 binds to DNA and changes conformation in the process. Such conformational changes are an important aspect of protein function and are displayed here as a dynamic computer-generated morph between two distinct structural states, which were determined experimentally. This video is available here: https://youtu.be/gY1p-xdHbQg

The ability to undergo quite radical conformational changes is complicating the development of pharmaceutical inhibitors for many nuclear proteins. New approaches are currently under way to explore how structurally less defined domains than the one displayed here can be targeted. Tobias Madl at the Medical University of Graz is one of the internationally leading researchers pioneering the development of targeting strategies for these type of proteins: https://mbbc.medunigraz.at/forschung/forschungseinheiten-und-gruppen/forschungsgruppe-tobias-madl/tobias-madl/

The structures used for the morph were:

C2IOI: Crystal structure of the mouse p53 core domain at 1.55 A DOI: 10.1107/S090744490603890X

3EXJ: Crystal Structure of a p53 Core Tetramer Bound to DNA DOI: 10.1038/onc.2008.400conformational changes o