Crystal structure of a p53 core tetramer bound to DNA.
The tumor suppressor p53 regulates downstream genes in response to many cellular stresses and is frequently mutated in human cancers. Here, we report the use of a crosslinking strategy to trap a tetrameric p53 DNA-binding domain (p53DBD) bound to DNA and the X-ray crystal structure of the protein/DNA complex. The structure reveals that two p53DBD dimers bind to B form DNA with no relative twist and that a p53 tetramer can bind to DNA without introducing significant DNA bending. The numerous dimer-dimer interactions involve several strictly conserved residues, thus suggesting a molecular basis for p53DBD-DNA binding cooperativity. Surface residue conservation of the p53DBD tetramer bound to DNA highlights possible regions of other p53 domain or p53 cofactor interactions.
Malecka
K A
KA
The Wistar Institute, Philadelphia, PA 19104, USA.
Ho
W C
WC
Marmorstein
R
R
D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004247:DNA