4GUQ: Structure Of Muts139f P73 Dna Binding Domain Complexed With 20bp Dna Response Element

Citation:
Abstract
Structural and biochemical studies have demonstrated that p73, p63 and p53 recognize DNA with identical amino acids and similar binding affinity. Here, measuring transactivation activity for a large number of response elements (REs) in yeast and human cell lines, we show that p53 family proteins also have overlapping transactivation profiles. We identified mutations at conserved amino acids of loops L1 and L3 in the DNA-binding domain that tune the transactivation potential nearly equally in p73, p63 and p53. For example, the mutant S139F in p73 has higher transactivation potential towards selected REs, enhanced DNA-binding cooperativity in vitro and a flexible loop L1 as seen in the crystal structure of the protein-DNA complex. By studying, how variations in the RE sequence affect transactivation specificity, we discovered a RE-transactivation code that predicts enhanced transactivation; this correlation is stronger for promoters of genes associated with apoptosis.
PDB ID: 4GUQDownload
MMDB ID: 112597
PDB Deposition Date: 2012/8/29
Updated in MMDB: 2013/10
Experimental Method:
x-ray diffraction
Resolution: 3.7  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4GUQ: tetrameric; determined by author
Molecular Components in 4GUQ
Label Count Molecule
Proteins (2 molecules)
2
Tumor Protein P73(Gene symbol: TP73)
Molecule annotation
Nucleotide(1 molecule)
2
DNA (5'-d(p*gp*ap*ap*cp*ap*tp*gp*tp*tp*c)-3')
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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