2b3g

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(New page: 200px<br /> <applet load="2b3g" size="450" color="white" frame="true" align="right" spinBox="true" caption="2b3g, resolution 1.60&Aring;" /> '''p53N (fragment 33-6...)
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[[Image:2b3g.gif|left|200px]]<br />
 
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<applet load="2b3g" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2b3g, resolution 1.60&Aring;" />
 
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'''p53N (fragment 33-60) bound to RPA70N'''<br />
 
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==Overview==
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==p53N (fragment 33-60) bound to RPA70N==
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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.
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<StructureSection load='2b3g' size='340' side='right'caption='[[2b3g]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2b3g]] is a 2 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B3G FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2b3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b3g OCA], [https://pdbe.org/2b3g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b3g RCSB], [https://www.ebi.ac.uk/pdbsum/2b3g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b3g ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/RFA1_HUMAN RFA1_HUMAN] Plays an essential role in several cellular processes in DNA metabolism including replication, recombination and DNA repair. Binds and subsequently stabilizes single-stranded DNA intermediates and thus prevents complementary DNA from reannealing.<ref>PMID:19116208</ref> <ref>PMID:19996105</ref> Functions as component of the alternative replication protein A complex (aRPA). aRPA binds single-stranded DNA and probably plays a role in DNA repair; it does not support chromosomal DNA replication and cell cycle progression through S-phase. In vitro, aRPA cannot promote efficient priming by DNA polymerase alpha but supports DNA polymerase delta synthesis in the presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange.<ref>PMID:19116208</ref> <ref>PMID:19996105</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b3/2b3g_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2b3g ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==Disease==
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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<ref>PMID:16234232</ref>
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Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Colorectal cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Hepatocellular carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Histiocytoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Li-Fraumeni syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Multiple malignancy syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Nasopharyngeal carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Osteosarcoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Pancreatic cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Thyroid carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2B3G OCA].
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</div>
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<div class="pdbe-citations 2b3g" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=16234232 16234232]
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*[[Single-stranded DNA-binding protein 3D structures|Single-stranded DNA-binding protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Arrowsmith, C.H.]]
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[[Category: Arrowsmith CH]]
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[[Category: Ayed, A.]]
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[[Category: Ayed A]]
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[[Category: Bochkarev, A.]]
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[[Category: Bochkarev A]]
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[[Category: Bochkareva, E.]]
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[[Category: Bochkareva E]]
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[[Category: Kaustov, L.]]
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[[Category: Kaustov L]]
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[[Category: Liao, J.C.]]
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[[Category: Liao JC]]
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[[Category: Lu, Y.]]
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[[Category: Lu Y]]
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[[Category: Milner, J.]]
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[[Category: Milner J]]
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[[Category: Okorokov, A.L.]]
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[[Category: Okorokov AL]]
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[[Category: Pineda-Lucena, A.]]
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[[Category: Pineda-Lucena A]]
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[[Category: Yi, G.S.]]
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[[Category: Yi GS]]
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[[Category: ob-fold]]
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[[Category: ssdna mimicry]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:57:49 2007''
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Current revision

p53N (fragment 33-60) bound to RPA70N

PDB ID 2b3g

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