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<StructureSection load='1ik9' size='340' side='right'caption='[[1ik9]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='1ik9' size='340' side='right'caption='[[1ik9]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1ik9]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. The July 2004 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''DNA Ligase''  by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2004_7 10.2210/rcsb_pdb/mom_2004_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IK9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1IK9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1ik9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The July 2004 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''DNA Ligase''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2004_7 10.2210/rcsb_pdb/mom_2004_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IK9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IK9 FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">XRCC4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LIG4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.3&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_ligase_(ATP) DNA ligase (ATP)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.5.1.1 6.5.1.1] </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=1ik9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ik9 OCA], [https://pdbe.org/1ik9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ik9 RCSB], [https://www.ebi.ac.uk/pdbsum/1ik9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ik9 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1ik9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ik9 OCA], [http://pdbe.org/1ik9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ik9 RCSB], [http://www.ebi.ac.uk/pdbsum/1ik9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ik9 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[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.
== Function ==
== Function ==
[[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> 
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=1ik9 ConSurf].
</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=1ik9 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A complex of two proteins, Xrcc4 and DNA ligase IV, plays a fundamental role in DNA non-homologous end joining (NHEJ), a cellular function required for double-strand break repair and V(D)J recombination. Here we report the crystal structure of human Xrcc4 bound to a polypeptide that corresponds to the DNA ligase IV sequence linking its two BRCA1 C-terminal (BRCT) domains. In the complex, a single ligase chain binds asymmetrically to an Xrcc4 dimer. The helical tails of Xrcc4 undergo a substantial conformational change relative to the uncomplexed protein, forming a coiled coil that unwinds upon ligase binding, leading to a flat interaction surface. A buried network of charged hydrogen bonds surrounded by extensive hydrophobic contacts explains the observed tightness of the interaction. The strong conservation of residues at the interface between the two proteins provides evidence that the observed mode of interaction has been maintained in NHEJ throughout evolution.
Crystal structure of an Xrcc4-DNA ligase IV complex.,Sibanda BL, Critchlow SE, Begun J, Pei XY, Jackson SP, Blundell TL, Pellegrini L Nat Struct Biol. 2001 Dec;8(12):1015-9. PMID:11702069<ref>PMID:11702069</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1ik9" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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</StructureSection>
</StructureSection>
[[Category: DNA Ligase]]
[[Category: DNA Ligase]]
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Begun, J]]
[[Category: Begun J]]
[[Category: Blundell, T L]]
[[Category: Blundell TL]]
[[Category: Critchlow, S E]]
[[Category: Critchlow SE]]
[[Category: Jackson, S P]]
[[Category: Jackson SP]]
[[Category: Pei, X Y]]
[[Category: Pei XY]]
[[Category: Pellegrini, L]]
[[Category: Pellegrini L]]
[[Category: Sibanda, B L]]
[[Category: Sibanda BL]]
[[Category: Coiled coil]]
[[Category: Dna end joining]]
[[Category: Double-strand break repair]]
[[Category: Gene regulation-ligase complex]]
[[Category: Protein-protein complex]]

Latest revision as of 10:36, 7 February 2024

CRYSTAL STRUCTURE OF A XRCC4-DNA LIGASE IV COMPLEXCRYSTAL STRUCTURE OF A XRCC4-DNA LIGASE IV COMPLEX

Structural highlights

1ik9 is a 3 chain structure with sequence from Homo sapiens. The July 2004 RCSB PDB Molecule of the Month feature on DNA Ligase by David S. Goodsell is 10.2210/rcsb_pdb/mom_2004_7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2] [3] [4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Li Z, Otevrel T, Gao Y, Cheng HL, Seed B, Stamato TD, Taccioli GE, Alt FW. The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination. Cell. 1995 Dec 29;83(7):1079-89. PMID:8548796
  2. ↑ Chen L, Trujillo K, Sung P, Tomkinson AE. Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase. J Biol Chem. 2000 Aug 25;275(34):26196-205. PMID:10854421 doi:10.1074/jbc.M000491200
  3. ↑ Nick McElhinny SA, Snowden CM, McCarville J, Ramsden DA. Ku recruits the XRCC4-ligase IV complex to DNA ends. Mol Cell Biol. 2000 May;20(9):2996-3003. PMID:10757784
  4. ↑ Foster RE, Nnakwe C, Woo L, Frank KM. Monoubiquitination of the nonhomologous end joining protein XRCC4. Biochem Biophys Res Commun. 2006 Mar 3;341(1):175-83. Epub 2006 Jan 6. PMID:16412978 doi:S0006-291X(05)02903-7

1ik9, resolution 2.30Å

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