2geq
From Proteopedia
Protein-DNA complex
Overview
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.
About this Structure
2GEQ is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Structure of the p53 core domain dimer bound to DNA., Ho WC, Fitzgerald MX, Marmorstein R, J Biol Chem. 2006 Jul 21;281(29):20494-502. Epub 2006 May 22. PMID:16717092 Page seeded by OCA on Sun May 4 05:01:10 2008
