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J. Biol. Chem., Vol. 281, Issue 29, 99923, July 21, 2006

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Trapped p53 Reveals Dimeric Structure

p53 is a transcription factor that regulates the cell cycle and thus functions as a tumor suppressor. It responds to cellular stresses such as DNA damage, in part, by binding to DNA and regulating the transcription of genes involved in cell cycle arrest, apoptosis, or senescence. In its active form, p53 forms a dimer of dimers. However, the only structural information about the mode of DNA recognition by p53 was provided over a decade ago when the structure of the p53 core domain monomer bound to DNA was determined.

Model of a p53DBD tetramer bound to icosamer DNA.

In this Paper of the Week, William C. Ho and colleagues use a cross-linking strategy to trap a p53 core domain dimer bound to DNA for structure determination by x-ray crystallography. Their 2.3 Å structure reveals the molecular details of cooperative dimeric p53 binding to DNA that involves a zinc-binding domain. The researchers also discovered that a hot spot for tumor-derived mutations maps to the dimerization region, reinforcing its functional importance. Interestingly, residues associated with p53 dimer formation on DNA are poorly conserved in the p63 and p73 paralogs, possibly due to their functional differences. Ho et al. also used the dimeric protein-DNA complex to model a dimer of p53 dimers bound to icosamer DNA. Their model suggests that the p53 core domain dimer-dimer contacts are less frequently mutated in human cancer than intra-dimer contacts.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 20494-20502

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Related Collections Papers Of The Week Social Bookmarking                      What's this?