2B29

N-terminal domain of the RPA70 subunit of human replication protein A.

Summary for 2B29

• Entry DOI: 10.2210/pdb2b29/pdb
• Descriptor: Replication protein A 70 kDa DNA-binding subunit (2 entities in total)
• Functional Keywords: replication
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P27694
• Total number of polymer chains: 1
• Total formula weight: 13469.65

Authors

Bochkareva, E.,Kaustov, L.,Ayed, A.,Okorokov, A.,Milner, J.,Arrowsmith, C.H.,Bochkarev, A. (deposition date: 2005-09-18, release date: 2005-10-04, Last modification date: 2024-02-14)

Primary citation

Bochkareva, E.,Kaustov, L.,Ayed, A.,Yi, G.S.,Lu, Y.,Pineda-Lucena, A.,Liao, J.C.,Okorokov, A.L.,Milner, J.,Arrowsmith, C.H.,Bochkarev, A.
Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A.
Proc.Natl.Acad.Sci.Usa, 102:15412-15417, 2005

PubMed Abstract: 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.

PubMed: 16234232
DOI: 10.1073/pnas.0504614102

Experimental method

X-RAY DIFFRACTION (1.6 Å)