Download Comparison of p53 Structure: Wild type vs. mutant

Comparison of p53 Structure:
Wild type vs. mutant
What change in wild type p53 may
lead to cancer?
Structure of Wild-type p53
1olg 
1tup 
Figure from Protein
Data Bank
1ycq 
Structural Domains of p53
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Composed of 4 polypeptide chains
Each chain has 3 domains
Tetramerization domain named 1olg
DNA binding domain named 1tup
Activation domain named 1ycg
Structure of DNA Binding domain is
highly conserved (purple)
Figure from ConSurf
Same
molecule
(1tup) as
ribbon
diagram
Figure from ConSurf
• Notice that the portion of the protein that
directly interacts with the DNA is highly
conserved (purple)
• Other protein regions are less highly
conserved
One amino
acid
substitution
from a
mutant p53
Figure from ConSurf
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)
Summary
• Mutations involving amino acids
substitutions in conserved domains can
negatively affect function of p53.
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