2r9a

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{{STRUCTURE_2r9a| PDB=2r9a | SCENE= }}
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==Crystal structure of human XLF==
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===Crystal structure of human XLF===
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<StructureSection load='2r9a' size='340' side='right' caption='[[2r9a]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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{{ABSTRACT_PUBMED_18158905}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2r9a]] is a 2 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=2R9A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2R9A FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NHEJ1, XLF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r9a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2r9a RCSB], [http://www.ebi.ac.uk/pdbsum/2r9a PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[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>
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== Function ==
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[[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r9/2r9a_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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DNA double-strand breaks represent one of the most severe forms of DNA damage in mammalian cells. One pathway for repairing these breaks occurs via nonhomologous end-joining (NHEJ) and depends on XRCC4, LigaseIV, and Cernunnos, also called XLF. Although XLF stimulates XRCC4/LigaseIV to ligate mismatched and noncohesive DNA ends, the mechanistic basis for this function remains unclear. Here we report the structure of a partially functional 224 residue N-terminal fragment of human XLF. Despite only weak sequence similarity, XLF(1-170) shares structural homology with XRCC4(1-159). However, unlike the highly extended 130 A helical domain observed in XRCC4, XLF adopts a more compact, folded helical C-terminal region involving two turns and a twist, wrapping back to the structurally conserved N terminus. Mutational analysis of XLF and XRCC4 reveals a potential interaction interface, suggesting a mechanism for how XLF stimulates the ligation of mismatched ends.
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==Disease==
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Crystal structure of human XLF: a twist in nonhomologous DNA end-joining.,Andres SN, Modesti M, Tsai CJ, Chu G, Junop MS Mol Cell. 2007 Dec 28;28(6):1093-101. PMID:18158905<ref>PMID:18158905</ref>
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[[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>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[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>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[2r9a]] is a 2 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=2R9A OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:018158905</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Andres, S N.]]
[[Category: Andres, S N.]]

Revision as of 19:39, 30 September 2014

Crystal structure of human XLF

2r9a, resolution 2.50Å

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