2b3g
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2b3g.gif|left|200px]] | + | [[Image:2b3g.gif|left|200px]] |
| - | + | ||
| - | '''p53N (fragment 33-60) bound to RPA70N''' | + | {{Structure |
| + | |PDB= 2b3g |SIZE=350|CAPTION= <scene name='initialview01'>2b3g</scene>, resolution 1.60Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= RPA1, REPA1, RPA70 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), TP53, P53 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''p53N (fragment 33-60) bound to RPA70N''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2B3G is a [ | + | 2B3G is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B3G OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16234232 16234232] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| Line 30: | Line 39: | ||
[[Category: ssdna mimicry]] | [[Category: ssdna mimicry]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:57:04 2008'' |
Revision as of 13:57, 20 March 2008
| |||||||
| , resolution 1.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | RPA1, REPA1, RPA70 (Homo sapiens), TP53, P53 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
p53N (fragment 33-60) bound to RPA70N
Contents |
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.
Disease
Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[191170], Breast cancer OMIM:[191170], Colorectal cancer OMIM:[191170], Hepatocellular carcinoma OMIM:[191170], Histiocytoma OMIM:[191170], Li-Fraumeni syndrome OMIM:[191170], Multiple malignancy syndrome OMIM:[191170], Nasopharyngeal carcinoma OMIM:[191170], Osteosarcoma OMIM:[191170], Pancreatic cancer OMIM:[191170], Thyroid carcinoma OMIM:[191170]
About this Structure
2B3G is a Protein complex structure of sequences 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
Page seeded by OCA on Thu Mar 20 15:57:04 2008
