4GUQ

Structure of mutS139F p73 DNA binding domain complexed with 20BP DNA response element

Summary for 4GUQ

• Entry DOI: 10.2210/pdb4guq/pdb
• Related: 4g82 4g83
• Descriptor: DNA (5'-D(P*GP*AP*AP*CP*AP*TP*GP*TP*TP*C)-3'), Tumor protein p73, ZINC ION (3 entities in total)
• Functional Keywords: tumor suppressor, beta-immunoglobulin, transcription factor, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O15350
• Total number of polymer chains: 4
• Total formula weight: 53890.95

Authors

Ethayathulla, A.S.,Nguyen, H.T.,Viadiu, H. (deposition date: 2012-08-29, release date: 2013-08-14, Last modification date: 2023-09-13)

Primary citation

Ciribilli, Y.,Monti, P.,Bisio, A.,Nguyen, H.T.,Ethayathulla, A.S.,Ramos, A.,Foggetti, G.,Menichini, P.,Menendez, D.,Resnick, M.A.,Viadiu, H.,Fronza, G.,Inga, A.
Transactivation specificity is conserved among p53 family proteins and depends on a response element sequence code.
Nucleic Acids Res., 41:8637-8653, 2013

PubMed 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.

PubMed: 23892287
DOI: 10.1093/nar/gkt657

Experimental method

X-RAY DIFFRACTION (3.7 Å)