Comparison of p53 Structure: Wild type vs. mutant

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Comparison of p53 StructureWild type vs. mutant

• What change in wild type p53 may lead to cancer?

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Structure of Wild-type p53
1olg ?
1tup ?
Figure from Protein Data Bank
1ycq ?
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Structural Domains of p53

• Composed of 4 polypeptide chains
• Each chain has 3 domains
• Tetramerization domain named 1olg
• DNA binding domain named 1tup
• Activation domain named 1ycg

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Structure of DNA Binding domain is highly
conserved (purple)
Figure from ConSurf
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Same molecule (1tup) as ribbon diagram
Figure from ConSurf
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• Notice that the portion of the protein that
  directly interacts with the DNA is highly
  conserved (purple)
• Other protein regions are less highly conserved

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One amino acid substitution from a mutant p53
Figure from ConSurf
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Protein Alignment of Wild-type p53 vs. mutant p53

• LRVEYLDDRNTFRHSVVVPYEPPEVGSD
• LRVEYLDDRNTFRHSVVVPYEPPEVGSE
• Summary Amino acid substitution D?E is from
  aspartate to glutatmate (both are negatively
  charged)

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Summary

• Mutations involving amino acids substitutions in
  conserved domains can negatively affect function
  of p53.

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Future Work

• Identify the specific amino acid locations in the
  1tup and determine if the mutations are in the
  highly conserved region and indicate these on our
  figures