1ik9

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[[Image:1ik9.png|left|200px]]
 
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{{STRUCTURE_1ik9| PDB=1ik9 | SCENE= }}
{{STRUCTURE_1ik9| PDB=1ik9 | SCENE= }}
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===CRYSTAL STRUCTURE OF A XRCC4-DNA LIGASE IV COMPLEX===
===CRYSTAL STRUCTURE OF A XRCC4-DNA LIGASE IV COMPLEX===
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{{ABSTRACT_PUBMED_11702069}}
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{{ABSTRACT_PUBMED_11702069}}
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==Disease==
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[[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.
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==Function==
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[[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>
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
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<ref group="xtra">PMID:011702069</ref><references group="xtra"/>
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<ref group="xtra">PMID:011702069</ref><references group="xtra"/><references/>
[[Category: DNA Ligase]]
[[Category: DNA Ligase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]

Revision as of 01:20, 25 March 2013

Template:STRUCTURE 1ik9

Contents

CRYSTAL STRUCTURE OF A XRCC4-DNA LIGASE IV COMPLEX

Template:ABSTRACT PUBMED 11702069

Disease

[DNLI4_HUMAN] Defects in LIG4 are the cause of LIG4 syndrome (LIG4S) [MIM: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.[1] 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: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

[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.[2][3][4][5] [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.[6][7]

About this Structure

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.

See Also

Reference

  • Sibanda BL, Critchlow SE, Begun J, Pei XY, Jackson SP, Blundell TL, Pellegrini L. Crystal structure of an Xrcc4-DNA ligase IV complex. Nat Struct Biol. 2001 Dec;8(12):1015-9. PMID:11702069 doi:10.1038/nsb725
  1. ↑ O'Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B, Hirsch B, Gennery A, Palmer SE, Seidel J, Gatti RA, Varon R, Oettinger MA, Neitzel H, Jeggo PA, Concannon P. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell. 2001 Dec;8(6):1175-85. PMID:11779494
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ Grawunder U, Zimmer D, Fugmann S, Schwarz K, Lieber MR. DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes. Mol Cell. 1998 Oct;2(4):477-84. PMID:9809069
  7. ↑ 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

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