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| {{STRUCTURE_3ii6| PDB=3ii6 | SCENE= }}
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| ===Structure of human Xrcc4 in complex with the tandem BRCT domains of DNA LigaseIV.===
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| {{ABSTRACT_PUBMED_19332554}}
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| ==Disease== | | ==Structure of human Xrcc4 in complex with the tandem BRCT domains of DNA LigaseIV.== |
| [[http://www.uniprot.org/uniprot/DNLI4_HUMAN DNLI4_HUMAN]] Defects in LIG4 are the cause of LIG4 syndrome (LIG4S) [MIM:[http://omim.org/entry/606593 606593]]. This disease is characterized by immunodeficiency and developmental and growth delay. Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and various skin abnormalities.<ref>PMID:11779494</ref> Defects in LIG4 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:[http://omim.org/entry/602450 602450]]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity. | | <StructureSection load='3ii6' size='340' side='right'caption='[[3ii6]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | | == Structural highlights == |
| ==Function== | | <table><tr><td colspan='2'>[[3ii6]] is a 6 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=3II6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3II6 FirstGlance]. <br> |
| [[http://www.uniprot.org/uniprot/XRCC4_HUMAN XRCC4_HUMAN]] Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. Binds to DNA and to DNA ligase IV (LIG4). The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.<ref>PMID:8548796</ref><ref>PMID:10854421</ref><ref>PMID:10757784</ref><ref>PMID:16412978</ref> [[http://www.uniprot.org/uniprot/DNLI4_HUMAN DNLI4_HUMAN]] Efficiently joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.<ref>PMID:9809069</ref><ref>PMID:10854421</ref> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| ==About this Structure==
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ii6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ii6 OCA], [https://pdbe.org/3ii6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ii6 RCSB], [https://www.ebi.ac.uk/pdbsum/3ii6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ii6 ProSAT]</span></td></tr> |
| [[3ii6]] is a 6 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=3II6 OCA].
| | </table> |
| | == Function == |
| | [https://www.uniprot.org/uniprot/XRCC4_HUMAN XRCC4_HUMAN] Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. Binds to DNA and to DNA ligase IV (LIG4). The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.<ref>PMID:8548796</ref> <ref>PMID:10854421</ref> <ref>PMID:10757784</ref> <ref>PMID:16412978</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/ii/3ii6_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=3ii6 ConSurf]. |
| | <div style="clear:both"></div> |
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| ==See Also== | | ==See Also== |
| *[[DNA ligase|DNA ligase]] | | *[[DNA ligase 3D structures|DNA ligase 3D structures]] |
| | | == References == |
| ==Reference== | | <references/> |
| <ref group="xtra">PMID:019332554</ref><references group="xtra"/><references/>
| | __TOC__ |
| | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Junop, M.]] | | [[Category: Large Structures]] |
| [[Category: Meesala, S.]] | | [[Category: Junop M]] |
| [[Category: Atp-binding]] | | [[Category: Meesala S]] |
| [[Category: Brct]]
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| [[Category: Cell cycle]]
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| [[Category: Cell division]]
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| [[Category: Disease mutation]]
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| [[Category: Dna damage]]
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| [[Category: Dna ligase iv]]
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| [[Category: Dna recombination]]
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| [[Category: Dna repair]]
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| [[Category: Dna replication]]
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| [[Category: Isopeptide bond]]
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| [[Category: Ligase]]
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| [[Category: Ligase-dna binding protein complex]]
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| [[Category: Magnesium]]
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| [[Category: Metal-binding]]
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| [[Category: Nhej]]
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| [[Category: Nucleotide-binding]]
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| [[Category: Nucleus]]
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| [[Category: Phosphoprotein]]
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| [[Category: Scid]]
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| [[Category: Xrcc4]]
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