2GEQ

Crystal Structure of a p53 Core Dimer Bound to DNA

Summary for 2GEQ

• Entry DOI: 10.2210/pdb2geq/pdb
• Descriptor: 5'-D(*GP*CP*GP*TP*GP*AP*GP*CP*AP*TP*GP*CP*TP*CP*AP*C)-3', Cellular tumor antigen p53, ZINC ION, ... (5 entities in total)
• Functional Keywords: protein-dna complex, tumor suppressor, transcription-dna complex, transcription/dna
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm (By similarity): P02340
• Total number of polymer chains: 4
• Total formula weight: 55801.58

Authors

Ho, W.C.,Fitzgerald, M.X.,Marmorstein, R. (deposition date: 2006-03-20, release date: 2006-05-23, Last modification date: 2023-08-30)

Primary citation

Ho, W.C.,Fitzgerald, M.X.,Marmorstein, R.
Structure of the p53 Core Domain Dimer Bound to DNA.
J.Biol.Chem., 281:20494-20502, 2006

PubMed Abstract: The p53 tumor suppressor protein binds to DNA as a dimer of dimers to regulate transcription of genes that mediate responses to cellular stress. We have prepared a cross-linked trapped p53 core domain dimer bound to decamer DNA and have determined its structure by x-ray crystallography to 2.3A resolution. The p53 core domain subunits bind nearly symmetrically to opposite faces of the DNA in a head-to-head fashion with a loophelix motif making sequence-specific DNA contacts and bending the DNA by about 20 degrees at the site of protein dimerization. Protein subunit interactions occur over the central DNA minor groove and involve residues from a zinc-binding region. Analysis of tumor derived p53 mutations reveals that the dimerization interface represents a third hot spot for mutation that also includes residues associated with DNA contact and protein stability. Residues associated with p53 dimer formation on DNA are poorly conserved in the p63 and p73 paralogs, possibly contributing to their functional differences. We have used the dimeric protein-DNA complex to model a dimer of p53 dimers bound to icosamer DNA that is consistent with solution bending data and suggests that p53 core domain dimer-dimer contacts are less frequently mutated in human cancer than intra-dimer contacts.

PubMed: 16717092
DOI: 10.1074/jbc.M603634200

Experimental method

X-RAY DIFFRACTION (2.3 Å)