TI  - Structure of the  <prot>p53</prot>  tumor suppressor bound to the ankyrin and SH3 domains
      of  <prot>53BP2</prot> .
PG  - 1001-5
AB  - Mutations in the <prot>p53</prot> tumor suppressor are among the most frequently
      observed genetic alterations in human cancer and map to the 200-amino acid
      core domain of the protein. The core domain contains the sequence-specific
      DNA binding activity and the in vitro  <prot>53BP2</prot>  protein binding activity of
       <prot>p53</prot> . The crystal structure of the  <prot>p53</prot>  core domain bound to the  <prot>53BP2</prot> 
      protein, which contains an SH3 (Src homology 3) domain and four ankyrin
      repeats, revealed that (i) the SH3 domain binds the L3 loop of <prot>p53</prot> in a
      manner distinct from that of previously characterized SH3-polyproline
      peptide complexes, and (ii) an ankyrin repeat, which forms an L-shaped
      structure consisting of a beta hairpin and two alpha helices, binds the L2
      loop of <prot>p53</prot>. The structure of the complex shows that the  <prot>53BP2</prot>  binding
      site on the  <prot>p53</prot>  core domain consists of evolutionarily conserved regions
      that are frequently mutated in cancer and that it overlaps the site of DNA
      binding. The six most frequently observed <prot>p53</prot> mutations disrupt <prot>53BP2</prot>
      binding in vitro. The structure provides evidence that the  <prot>53BP2</prot> - <prot>p53</prot> 
      complex forms in vivo and may have a critical role in the <prot>p53</prot> pathway of
      tumor suppression.
AD  - Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering
