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| | <StructureSection load='3i8c' size='340' side='right'caption='[[3i8c]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='3i8c' size='340' side='right'caption='[[3i8c]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3i8c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I8C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I8C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3i8c]] 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=3I8C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I8C FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2b5m|2b5m]], [[3i7h|3i7h]], [[3i7k|3i7k]], [[3i7l|3i7l]], [[3i7n|3i7n]], [[3i7o|3i7o]], [[3i7p|3i7p]], [[3i89|3i89]], [[3i8e|3i8e]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DDB1, XAP1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3i8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i8c OCA], [https://pdbe.org/3i8c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i8c RCSB], [https://www.ebi.ac.uk/pdbsum/3i8c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i8c ProSAT]</span></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=3i8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i8c OCA], [https://pdbe.org/3i8c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i8c RCSB], [https://www.ebi.ac.uk/pdbsum/3i8c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i8c ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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> [[https://www.uniprot.org/uniprot/DCAF4_HUMAN DCAF4_HUMAN]] May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.<ref>PMID:16949367</ref> <ref>PMID:16964240</ref>
| + | [https://www.uniprot.org/uniprot/DCAF4_HUMAN DCAF4_HUMAN] May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.<ref>PMID:16949367</ref> <ref>PMID:16964240</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i8/3i8c_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i8/3i8c_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Breugel, P C.V]] | + | [[Category: Breugel PCV]] |
| - | [[Category: Li, T]] | + | [[Category: Li T]] |
| - | [[Category: Robert, E I]] | + | [[Category: Robert EI]] |
| - | [[Category: Strubin, M]] | + | [[Category: Strubin M]] |
| - | [[Category: Zheng, N]] | + | [[Category: Zheng N]] |
| - | [[Category: Alternative splicing]]
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| - | [[Category: Cytoplasm]]
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| - | [[Category: Dcaf4]]
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| - | [[Category: Ddb1]]
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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: Polymorphism]]
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| - | [[Category: Protein binding]]
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| - | [[Category: Ubl conjugation]]
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| - | [[Category: Ubl conjugation pathway]]
| + | |
| - | [[Category: Wd repeat]]
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| - | [[Category: Wdr21a]]
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| Structural highlights
Function
DCAF4_HUMAN May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jin J, Arias EE, Chen J, Harper JW, Walter JC. A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol Cell. 2006 Sep 1;23(5):709-21. PMID:16949367 doi:http://dx.doi.org/S1097-2765(06)00570-3
- ↑ Angers S, Li T, Yi X, MacCoss MJ, Moon RT, Zheng N. Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature. 2006 Oct 5;443(7111):590-3. PMID:16964240 doi:10.1038/nature05175
- ↑ Li T, Robert EI, van Breugel PC, Strubin M, Zheng N. A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery. Nat Struct Mol Biol. 2010 Jan;17(1):105-11. Epub 2009 Dec 6. PMID:19966799 doi:10.1038/nsmb.1719
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