2b3g
From Proteopedia
(New page: 200px<br /> <applet load="2b3g" size="450" color="white" frame="true" align="right" spinBox="true" caption="2b3g, resolution 1.60Å" /> '''p53N (fragment 33-6...) |
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| - | [[Image:2b3g.gif|left|200px]]<br /> | + | [[Image:2b3g.gif|left|200px]]<br /><applet load="2b3g" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2b3g" size=" | + | |
caption="2b3g, resolution 1.60Å" /> | caption="2b3g, resolution 1.60Å" /> | ||
'''p53N (fragment 33-60) bound to RPA70N'''<br /> | '''p53N (fragment 33-60) bound to RPA70N'''<br /> | ||
==Overview== | ==Overview== | ||
| - | One of many protein-protein interactions modulated upon DNA damage is that | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2B3G is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2B3G is a [http://en.wikipedia.org/wiki/Protein_complex 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== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Arrowsmith, C | + | [[Category: Arrowsmith, C H.]] |
[[Category: Ayed, A.]] | [[Category: Ayed, A.]] | ||
[[Category: Bochkarev, A.]] | [[Category: Bochkarev, A.]] | ||
[[Category: Bochkareva, E.]] | [[Category: Bochkareva, E.]] | ||
[[Category: Kaustov, L.]] | [[Category: Kaustov, L.]] | ||
| - | [[Category: Liao, J | + | [[Category: Liao, J C.]] |
[[Category: Lu, Y.]] | [[Category: Lu, Y.]] | ||
[[Category: Milner, J.]] | [[Category: Milner, J.]] | ||
| - | [[Category: Okorokov, A | + | [[Category: Okorokov, A L.]] |
[[Category: Pineda-Lucena, A.]] | [[Category: Pineda-Lucena, A.]] | ||
| - | [[Category: Yi, G | + | [[Category: Yi, G S.]] |
[[Category: ob-fold]] | [[Category: ob-fold]] | ||
[[Category: ssdna mimicry]] | [[Category: ssdna mimicry]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:33:44 2008'' |
Revision as of 14:33, 21 February 2008
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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
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