p53 (L14) Flashcards
How does p53 inhibit tumor formation?
Through maintenance of the genome integrity during the cell cycle
What is an important function of tumor suppressor genes?
Control of cell proliferation by regulating the mechanism of progression through the cell cycle
What is the p53 sequence?
3 domains each with its own function
N-terminal activation domain
DNA binding domain
C-terminal forms an oligodimerisation domain
What is the structure of the p53 oligodimerisation domain?
beta strand-turn-alpha helix motif
The turn at the end of the beta strand comprises a single glycine residue in a conformation only allowed for glycine
What mutations can occur in the oligodimerisation domain?
Leu330-His330 which disrupts the hydrophobic core and thus prevent dimer formation and the mutation of Gly in turn. Incorrect folding for dimerisation
What is the structure of the p53 DNA-binding domain?
Antiparallel beta barrel scaffold with the DNA
Binding loops protruding from the more open end of the barrel
C-terminal alpha helix
Long loops
SLH region
How are the L2 and L3 loops stabilised?
A zinc atom which is bound to 2 cysteine side chains from L3 and one from L2
Describe the topology of the p53 DNA-binding domain
Nine antiparallel beta strands form a beta barrel
Beta-strands 4 and 5 are short and are at the edges of the beta sheets that build the beta barrel
Remaining seven strands have the immunoglobulin fold
Describe the topology of the p53 constant Ig domain
The seven stranded antiparallel beta barrel is formed from two beta sheets B1-B2-B3-B4 and B3-B6-B7
Describe the topology of the p53 antiparallel beta barrel
The seven beta strands of p53 which have the Ig fold
Describe the structure of the p53-DNA complex
SLH, L1 and L3 make sequence specific contacts with the DNA
The C-terminal helix and L1 bind in the major groove of DNA, with Arg280 from the helix and Lys120 from L1 forming specific interactions with DNA bases
Arg248 from loop L3 binds to the DNA in the minor groove
