2b3g
From Proteopedia
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| - | [[Image:2b3g.gif|left|200px]]<br /><applet load="2b3g" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2b3g, resolution 1.60Å" /> | ||
| - | '''p53N (fragment 33-60) bound to RPA70N'''<br /> | ||
| - | == | + | ==p53N (fragment 33-60) bound to RPA70N== |
| + | <StructureSection load='2b3g' size='340' side='right'caption='[[2b3g]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <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> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | ||
| + | <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> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b3/2b3g_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
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. | 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. | ||
| - | + | 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> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 2b3g" style="background-color:#fffaf0;"></div> | ||
| - | == | + | ==See Also== |
| - | Single-stranded DNA | + | *[[Single-stranded DNA-binding protein 3D structures|Single-stranded DNA-binding protein 3D structures]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Ayed | + | [[Category: Ayed A]] |
| - | [[Category: Bochkarev | + | [[Category: Bochkarev A]] |
| - | [[Category: Bochkareva | + | [[Category: Bochkareva E]] |
| - | [[Category: Kaustov | + | [[Category: Kaustov L]] |
| - | [[Category: Liao | + | [[Category: Liao JC]] |
| - | [[Category: Lu | + | [[Category: Lu Y]] |
| - | [[Category: Milner | + | [[Category: Milner J]] |
| - | [[Category: Okorokov | + | [[Category: Okorokov AL]] |
| - | [[Category: Pineda-Lucena | + | [[Category: Pineda-Lucena A]] |
| - | [[Category: Yi | + | [[Category: Yi GS]] |
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Current revision
p53N (fragment 33-60) bound to RPA70N
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Categories: Homo sapiens | Large Structures | Arrowsmith CH | Ayed A | Bochkarev A | Bochkareva E | Kaustov L | Liao JC | Lu Y | Milner J | Okorokov AL | Pineda-Lucena A | Yi GS
