Interaction of the p53 DNA-binding domain with its n-terminal extension modulates the stability of the p53 tetramer.

ABSTRACT: The tetrameric tumor suppressor p53 plays a pivotal role in the control of the cell cycle and provides a paradigm for an emerging class of oligomeric, multidomain proteins with structured and intrinsically disordered regions. Many of its biophysical and functional properties have been extrapolated from truncated variants, yet the exact structural and functional role of certain segments of the protein is unclear. We found from NMR and X-ray crystallography that the DNA-binding domain (DBD) of human p53, usually defined as residues 94-292, extends beyond these domain boundaries. Trp91, in the hinge region between the disordered proline-rich N-terminal domain and the DBD, folds back onto the latter and has a cation-π interaction with Arg174. These additional interactions increase the melting

SUBMITTER: Natan E 

PROVIDER: S-EPMC3176915 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature