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| - | {{STRUCTURE_3sr2| PDB=3sr2 | SCENE= }} | |
| - | ===Crystal Structure of Human XLF-XRCC4 Complex=== | |
| - | {{ABSTRACT_PUBMED_21775435}} | |
| | | | |
| - | ==Disease== | + | ==Crystal Structure of Human XLF-XRCC4 Complex== |
| - | [[http://www.uniprot.org/uniprot/NHEJ1_HUMAN NHEJ1_HUMAN]] Defects in NHEJ1 are the cause of severe combined immunodeficiency due to NHEJ1 deficiency (NHEJ1-SCID) [MIM:[http://omim.org/entry/611291 611291]]; also known as autosomal recessive T-cell-negative, B-cell-negative, NK cell-positive, severe combined immunodeficiency with microcephaly, growth retardation and sensitivity to ionizing radiation or NHEJ1 syndrome. 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. NHEJ1-SCID is characterized by a profound T- and B-lymphocytopenia associated with increased cellular sensitivity to ionizing radiation, microcephaly and growth retardation. Some patients may manifest SCID with sensitivity to ionizing radiation without microcephaly and mild growth retardation, probably due to hypomorphic NHEJ1 mutations.<ref>PMID:16439204</ref><ref>PMID:16439205</ref><ref>PMID:17317666</ref><ref>PMID:12604777</ref> Note=A chromosomal aberration involving NHEJ1 is found in a patient with polymicrogyria. Translocation t(2;7)(q35;p22).<ref>PMID:12604777</ref> | + | <StructureSection load='3sr2' size='340' side='right'caption='[[3sr2]], [[Resolution|resolution]] 3.97Å' scene=''> |
| - | | + | == Structural highlights == |
| - | ==Function== | + | <table><tr><td colspan='2'>[[3sr2]] is a 8 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=3SR2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SR2 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/NHEJ1_HUMAN NHEJ1_HUMAN]] DNA repair protein involved in DNA nonhomologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. May serve as a bridge between XRCC4 and the other NHEJ factors located at DNA ends, or may participate in reconfiguration of the end bound NHEJ factors to allow XRCC4 access to the DNA termini. It may act in concert with XRCC6/XRCC5 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are noncomplementary or partially complementary.<ref>PMID:16439204</ref><ref>PMID:16439205</ref><ref>PMID:17470781</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]] 3.9708Å</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=3sr2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sr2 OCA], [https://pdbe.org/3sr2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sr2 RCSB], [https://www.ebi.ac.uk/pdbsum/3sr2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sr2 ProSAT]</span></td></tr> |
| - | ==About this Structure== | + | </table> |
| - | [[3sr2]] is a 8 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=3SR2 OCA].
| + | == 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> |
| - | ==Reference==
| + | == References == |
| - | <ref group="xtra">PMID:021775435</ref><references group="xtra"/><references/>
| + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Classen, S.]] | + | [[Category: Large Structures]] |
| - | [[Category: Hammel, M.]] | + | [[Category: Classen S]] |
| - | [[Category: Tainer, J A.]] | + | [[Category: Hammel M]] |
| - | [[Category: Complex]] | + | [[Category: Tainer JA]] |
| - | [[Category: Dimerization]]
| + | |
| - | [[Category: Dna]]
| + | |
| - | [[Category: Dna binding protein-protein binding complex]]
| + | |
| - | [[Category: Dna ligase iv]]
| + | |
| - | [[Category: Dna ligase]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Dna-binding protein]]
| + | |
| - | [[Category: Human]]
| + | |
| - | [[Category: Ku]]
| + | |
| - | [[Category: Nhej]]
| + | |
| - | [[Category: Protein dna-interaction]]
| + | |
| - | [[Category: Protein structure]]
| + | |
| - | [[Category: Quaternary]]
| + | |
| - | [[Category: Xlf]]
| + | |
| - | [[Category: Xlf-xrcc4]]
| + | |
| - | [[Category: Xrcc4]]
| + | |
| Structural highlights
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]
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
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