3i7l

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{{STRUCTURE_3i7l| PDB=3i7l | SCENE= }}
 
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===Crystal Structure of DDB1 in Complex with the H-Box Motif of DDB2===
 
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{{ABSTRACT_PUBMED_19966799}}
 
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==Disease==
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==Crystal Structure of DDB1 in Complex with the H-Box Motif of DDB2==
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[[http://www.uniprot.org/uniprot/DDB2_HUMAN DDB2_HUMAN]] Defects in DDB2 are a cause of xeroderma pigmentosum complementation group E (XP-E) [MIM:[http://omim.org/entry/278740 278740]]; also known as xeroderma pigmentosum V (XP5). XP-E is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.<ref>PMID:8798680</ref>
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<StructureSection load='3i7l' size='340' side='right'caption='[[3i7l]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3i7l]] 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=3I7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I7L 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]] 2.8&#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=3i7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i7l OCA], [https://pdbe.org/3i7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i7l RCSB], [https://www.ebi.ac.uk/pdbsum/3i7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i7l ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DDB1_HUMAN DDB1_HUMAN] Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2.<ref>PMID:12732143</ref> <ref>PMID:15448697</ref> <ref>PMID:14739464</ref> <ref>PMID:15882621</ref> <ref>PMID:16260596</ref> <ref>PMID:16482215</ref> <ref>PMID:17079684</ref> <ref>PMID:16407242</ref> <ref>PMID:16407252</ref> <ref>PMID:16678110</ref> <ref>PMID:16940174</ref> <ref>PMID:17041588</ref> <ref>PMID:16473935</ref> <ref>PMID:18593899</ref> <ref>PMID:18381890</ref> <ref>PMID:18332868</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/i7/3i7l_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3i7l 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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The cullin 4-DNA-damage-binding protein 1 (CUL4-DDB1) ubiquitin ligase machinery regulates diverse cellular functions and can be subverted by pathogenic viruses. Here we report the crystal structure of DDB1 in complex with a central fragment of hepatitis B virus X protein (HBx), whose DDB1-binding activity is important for viral infection. The structure reveals that HBx binds DDB1 through an alpha-helical motif, which is also found in the unrelated paramyxovirus SV5-V protein despite their sequence divergence. Our structure-based functional analysis suggests that, like SV5-V, HBx captures DDB1 to redirect the ubiquitin ligase activity of the CUL4-DDB1 E3 ligase. We also identify the alpha-helical motif shared by these viral proteins in the cellular substrate-recruiting subunits of the E3 complex, the DDB1-CUL4-associated factors (DCAFs) that are functionally mimicked by the viral hijackers. Together, our studies reveal a common yet promiscuous structural element that is important for the assembly of cellular and virally hijacked CUL4-DDB1 E3 complexes.
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==Function==
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A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery.,Li T, Robert EI, van Breugel PC, Strubin M, Zheng N Nat Struct Mol Biol. 2010 Jan;17(1):105-11. Epub 2009 Dec 6. PMID:19966799<ref>PMID:19966799</ref>
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[[http://www.uniprot.org/uniprot/DDB1_HUMAN DDB1_HUMAN]] Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2.<ref>PMID:12732143</ref><ref>PMID:15448697</ref><ref>PMID:14739464</ref><ref>PMID:15882621</ref><ref>PMID:16260596</ref><ref>PMID:16482215</ref><ref>PMID:17079684</ref><ref>PMID:16407242</ref><ref>PMID:16407252</ref><ref>PMID:16678110</ref><ref>PMID:16940174</ref><ref>PMID:17041588</ref><ref>PMID:16473935</ref><ref>PMID:18593899</ref><ref>PMID:18381890</ref><ref>PMID:18332868</ref> [[http://www.uniprot.org/uniprot/DDB2_HUMAN DDB2_HUMAN]] Required for DNA repair. Binds to DDB1 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as the substrate recognition module for the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB1-CUL4-ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. The DDB1-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. Isoform D1 and isoform D2 inhibit UV-damaged DNA repair.<ref>PMID:14751237</ref><ref>PMID:9892649</ref><ref>PMID:10882109</ref><ref>PMID:11278856</ref><ref>PMID:11705987</ref><ref>PMID:12732143</ref><ref>PMID:12944386</ref><ref>PMID:15882621</ref><ref>PMID:16260596</ref><ref>PMID:16678110</ref><ref>PMID:16473935</ref><ref>PMID:18593899</ref>
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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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[[3i7l]] is a 2 chain structure with sequence 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=3I7L OCA].
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</div>
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<div class="pdbe-citations 3i7l" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:019966799</ref><references group="xtra"/><references/>
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*[[DNA damage-binding protein|DNA damage-binding protein]]
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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: Breugel, P C.V.]]
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[[Category: Large Structures]]
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[[Category: Li, T.]]
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[[Category: Breugel PCV]]
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[[Category: Robert, E I.]]
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[[Category: Li T]]
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[[Category: Strubin, M.]]
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[[Category: Robert EI]]
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[[Category: Zheng, N.]]
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[[Category: Strubin M]]
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[[Category: Ddb1]]
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[[Category: Zheng N]]
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[[Category: Ddb2]]
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[[Category: Disease mutation]]
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[[Category: Dna damage]]
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[[Category: Dna repair]]
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[[Category: Dna-binding]]
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[[Category: H-box motif]]
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[[Category: Host-virus interaction]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Protein binding]]
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[[Category: Ubl conjugation pathway]]
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[[Category: Wd repeat]]
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[[Category: Xeroderma pigmentosum]]
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Current revision

Crystal Structure of DDB1 in Complex with the H-Box Motif of DDB2

PDB ID 3i7l

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