3VD2

structure of p73 DNA binding domain tetramer modulates p73 transactivation

Summary for 3VD2

• Entry DOI: 10.2210/pdb3vd2/pdb
• Related: 3VD0 3VD1
• Descriptor: Tumor protein p73, DNA (5'-D(*AP*TP*GP*GP*AP*CP*AP*TP*GP*TP*CP*CP*AP*T)-3'), ZINC ION (3 entities in total)
• Functional Keywords: protein dna complex, beta-immunoglobulin-like fold, tumour suppressor, dna, antitumor protein-dna complex, antitumor protein/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O15350
• Total number of polymer chains: 12
• Total formula weight: 168727.01

Authors

Ethayathulla, A.S.,Tse, P.W.,Nguyen, S.,Viadiu, H. (deposition date: 2012-01-04, release date: 2012-04-18, Last modification date: 2024-10-30)

Primary citation

Ethayathulla, A.S.,Tse, P.W.,Monti, P.,Nguyen, S.,Inga, A.,Fronza, G.,Viadiu, H.
Structure of p73 DNA-binding domain tetramer modulates p73 transactivation.
Proc.Natl.Acad.Sci.USA, 109:6066-6071, 2012

PubMed 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.

PubMed: 22474346
DOI: 10.1073/pnas.1115463109

Experimental method

X-RAY DIFFRACTION (4 Å)