2b29
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(New page: 200px<br /> <applet load="2b29" size="450" color="white" frame="true" align="right" spinBox="true" caption="2b29, resolution 1.60Å" /> '''N-terminal domain o...)
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Revision as of 18:51, 12 November 2007
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N-terminal domain of the RPA70 subunit of human replication protein A.
Overview
One of many protein-protein interactions modulated upon DNA damage is that, of the single-stranded DNA-binding protein, replication protein A (RPA), with the p53 tumor suppressor. Here we report the crystal structure of RPA, residues 1-120 (RPA70N) bound to the N-terminal transactivation domain of, p53 (residues 37-57; p53N) and, by using NMR spectroscopy, characterize, two mechanisms by which the RPA/p53 interaction can be modulated. RPA70N, forms an oligonucleotide/oligosaccharide-binding fold, similar to that, previously observed for the ssDNA-binding domains of RPA. In contrast, the, N-terminal p53 transactivation domain is largely disordered in solution, but residues 37-57 fold into two amphipathic helices, H1 and H2, upon, binding with RPA70N. The H2 helix of p53 structurally mimics the binding, of ssDNA to the oligonucleotide/oligosaccharide-binding fold. NMR, experiments confirmed that both ssDNA and an acidic peptide mimicking a, phosphorylated form of RPA32N can independently compete the acidic p53N, out of the binding site. Taken together, our data suggest a mechanism for, DNA damage signaling that can explain a threshold response to DNA damage.
About this Structure
2B29 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A., Bochkareva E, Kaustov L, Ayed A, Yi GS, Lu Y, Pineda-Lucena A, Liao JC, Okorokov AL, Milner J, Arrowsmith CH, Bochkarev A, Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15412-7. Epub 2005 Oct 17. PMID:16234232
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