3VD2: Structure Of P73 Dna Binding Domain Tetramer Modulates P73 Transactivation

Citation:
Abstract
The transcription factor p73 triggers developmental pathways and overlaps stress-induced p53 transcriptional pathways. How p53-family response elements determine and regulate transcriptional specificity remains an unsolved problem. In this work, we have determined the first crystal structures of p73 DNA-binding domain tetramer bound to response elements with spacers of different length. The structure and function of the adaptable tetramer are determined by the distance between two half-sites. The structures with zero and one base-pair spacers show compact p73 DNA-binding domain tetramers with large tetramerization interfaces; a two base-pair spacer results in DNA unwinding and a smaller tetramerization interface, whereas a four base-pair spacer hinders tetramerization. Functionally, p73 is more sensitive to spacer length than p53, with one base-pair spacer reducing 90% of transactivation activity and longer spacers reducing transactivation to basal levels. Our results establish the quaternary structure of the p73 DNA-binding domain required as a scaffold to promote transactivation.
PDB ID: 3VD2Download
MMDB ID: 98845
PDB Deposition Date: 2012/1/4
Updated in MMDB: 2012/08
Experimental Method:
x-ray diffraction
Resolution: 4  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3VD2: octameric; determined by author
Molecular Components in 3VD2
Label Count Molecule
Proteins (4 molecules)
4
Tumor Protein P73(Gene symbol: TP73)
Molecule annotation
Nucleotide(1 molecule)
4
DNA (5'-d(*ap*tp*gp*gp*ap*cp*ap*tp*gp*tp*cp*cp*ap*t)-3')
Molecule annotation
Chemicals (4 molecules)
1
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.