p53
p53 is a tumor suppressor
- normally, its levels are low
- when DNA damage is detected, p53 is made
- p53 then binds to many regulatory sites on the genome until the damage is repaired
- if unable to repair, p53 initiates apoptosis
- p53 tumor suppressor is a flexible molecule composed of four identical protein chains
- it is destroyed by MDM2 which is a ubiquitin ligase
- PDB101 entry
- 1tup
Mutations
Most of the p53 mutations that cause cancer are found in the DNA-binding domain. The most common mutations are shown here, using PDB entry 1tup. This PDB entry includes three copies of the DNA-binding domain; only one (chain B in the file) is shown here. The mutations are found in and around the DNA-binding face of the protein. The most common mutation changes arginine 248, colored red here. Notice how it snakes into the minor groove of the DNA (shown in blue and green), forming a strong stabilizing interaction. When mutated to another amino acid, this interaction is lost. Other key sites of mutation are shown in pink, including arginine residues 175, 249, 273 and 282, and glycine 245.