3w1g - Revision history

OCA at 12:45, 8 November 2023

2023-11-08T12:45:35Z

←Older revision		Revision as of 12:45, 8 November 2023
Line 3:		Line 3:
	<StructureSection load='3w1g' size='340' side='right'caption='[[3w1g]], [[Resolution\|resolution]] 2.55Å' scene=''>		<StructureSection load='3w1g' size='340' side='right'caption='[[3w1g]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3w1g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W1G FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3w1g]] is a 2 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=3W1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W1G FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ATP:ADENOSINE~~-~~5-TRIPHOSPHATE'>ATP</scene>~~, ~~<scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.55Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[3w1b\|3w1b]], [[3vnn\|3vnn]], [[1ik9\|1ik9]], [[3ii6\|3ii6]], [[2e2w\|2e2w]], [[1x9n\|1x9n]], [[3w5o\|3w5o]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>LIG4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</td~~><~~/tr>~~	+
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[https://en.wikipedia.org/wiki/DNA_ligase_(ATP) DNA ligase (ATP)], with EC number [https://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=3w1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w1g OCA], [https://pdbe.org/3w1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w1g RCSB], [https://www.ebi.ac.uk/pdbsum/3w1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w1g ProSAT]</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=3w1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w1g OCA], [https://pdbe.org/3w1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w1g RCSB], [https://www.ebi.ac.uk/pdbsum/3w1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w1g ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/DNLI4_HUMAN DNLI4_HUMAN]] Defects in LIG4 are the cause of LIG4 syndrome (LIG4S) [MIM:[https://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:[https://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. [[https://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Severe combined immunodeficiency, alymphocytotic type;Omenn syndrome. Defects in DCLRE1C 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:[https://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.<ref>PMID:11336668</ref> <ref>PMID:12406895</ref> <ref>PMID:12921762</ref> <ref>PMID:12592555</ref> <ref>PMID:12569164</ref> Defects in DCLRE1C are the cause of severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:[https://omim.org/entry/602450 602450]]. SCIDA is a variety of RS-SCID caused by a founder mutation in Athabascan-speaking native Americans, being inherited as an autosomal recessive trait with an estimated gene frequency of 2.1% in the Navajo population. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID.<ref>PMID:12055248</ref> Defects in DCLRE1C are a cause of Omenn syndrome (OS) [MIM:[https://omim.org/entry/603554 603554]]. OS is characterized by severe combined immunodeficiency associated with erythrodermia, hepatosplenomegaly, lymphadenopathy and alopecia. Affected individuals have elevated T-lymphocyte counts with a restricted T-cell receptor (TCR) repertoire. They also generally lack B-lymphocytes, but have normal natural killer (NK) cell function (T+ B- NK+).	+	[https://www.uniprot.org/uniprot/DNLI4_HUMAN DNLI4_HUMAN] Defects in LIG4 are the cause of LIG4 syndrome (LIG4S) [MIM:[https://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:[https://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 ==
-	[[https://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/DCR1C_HUMAN DCR1C_HUMAN]] Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC. The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint. May also be required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ.<ref>PMID:11336668</ref> <ref>PMID:12055248</ref> <ref>PMID:11955432</ref> <ref>PMID:15071507</ref> <ref>PMID:15468306</ref> <ref>PMID:14744996</ref> <ref>PMID:15574326</ref> <ref>PMID:15574327</ref> <ref>PMID:15456891</ref> <ref>PMID:15811628</ref> <ref>PMID:15936993</ref>	+	[https://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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Blundell~~, T L~~]]	+	[[Category: Blundell TL]]
-	[[Category: Ochi, T]]	+	[[Category: Ochi T]]
-	~~[[Category: Dna ligase]]~~	+
-	~~[[Category: Dna repair]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Non homologous end joining]]~~	+
-	~~[[Category: Xrcc4~~]]	+

OCA at 05:18, 3 August 2022

2022-08-03T05:18:06Z

←Older revision		Revision as of 05:18, 3 August 2022
Line 1:		Line 1:

	==Crystal Structure of Human DNA ligase IV-Artemis Complex (Native)==		==Crystal Structure of Human DNA ligase IV-Artemis Complex (Native)==
-	<StructureSection load='3w1g' size='340' side='right' caption='[[3w1g]], [[Resolution\|resolution]] 2.55Å' scene=''>	+	<StructureSection load='3w1g' size='340' side='right'caption='[[3w1g]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3w1g]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1G OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3W1G FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3w1g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W1G FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3w1b\|3w1b]], [[3vnn\|3vnn]], [[1ik9\|1ik9]], [[3ii6\|3ii6]], [[2e2w\|2e2w]], [[1x9n\|1x9n]], [[3w5o\|3w5o]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3w1b\|3w1b]], [[3vnn\|3vnn]], [[1ik9\|1ik9]], [[3ii6\|3ii6]], [[2e2w\|2e2w]], [[1x9n\|1x9n]], [[3w5o\|3w5o]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LIG4 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LIG4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/DNA_ligase_(ATP) DNA ligase (ATP)], with EC number [https://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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3w1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w1g OCA], [~~http~~://pdbe.org/3w1g PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3w1g RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3w1g PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3w1g ProSAT]</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=3w1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w1g OCA], [https://pdbe.org/3w1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w1g RCSB], [https://www.ebi.ac.uk/pdbsum/3w1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w1g ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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. [[~~http~~://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Severe combined immunodeficiency, alymphocytotic type;Omenn syndrome. Defects in DCLRE1C 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.<ref>PMID:11336668</ref> <ref>PMID:12406895</ref> <ref>PMID:12921762</ref> <ref>PMID:12592555</ref> <ref>PMID:12569164</ref> Defects in DCLRE1C are the cause of severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:[~~http~~://omim.org/entry/602450 602450]]. SCIDA is a variety of RS-SCID caused by a founder mutation in Athabascan-speaking native Americans, being inherited as an autosomal recessive trait with an estimated gene frequency of 2.1% in the Navajo population. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID.<ref>PMID:12055248</ref> Defects in DCLRE1C are a cause of Omenn syndrome (OS) [MIM:[~~http~~://omim.org/entry/603554 603554]]. OS is characterized by severe combined immunodeficiency associated with erythrodermia, hepatosplenomegaly, lymphadenopathy and alopecia. Affected individuals have elevated T-lymphocyte counts with a restricted T-cell receptor (TCR) repertoire. They also generally lack B-lymphocytes, but have normal natural killer (NK) cell function (T+ B- NK+).	+	[[https://www.uniprot.org/uniprot/DNLI4_HUMAN DNLI4_HUMAN]] Defects in LIG4 are the cause of LIG4 syndrome (LIG4S) [MIM:[https://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:[https://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. [[https://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Severe combined immunodeficiency, alymphocytotic type;Omenn syndrome. Defects in DCLRE1C 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:[https://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.<ref>PMID:11336668</ref> <ref>PMID:12406895</ref> <ref>PMID:12921762</ref> <ref>PMID:12592555</ref> <ref>PMID:12569164</ref> Defects in DCLRE1C are the cause of severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:[https://omim.org/entry/602450 602450]]. SCIDA is a variety of RS-SCID caused by a founder mutation in Athabascan-speaking native Americans, being inherited as an autosomal recessive trait with an estimated gene frequency of 2.1% in the Navajo population. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID.<ref>PMID:12055248</ref> Defects in DCLRE1C are a cause of Omenn syndrome (OS) [MIM:[https://omim.org/entry/603554 603554]]. OS is characterized by severe combined immunodeficiency associated with erythrodermia, hepatosplenomegaly, lymphadenopathy and alopecia. Affected individuals have elevated T-lymphocyte counts with a restricted T-cell receptor (TCR) repertoire. They also generally lack B-lymphocytes, but have normal natural killer (NK) cell function (T+ B- NK+).
	== Function ==		== Function ==
-	[[~~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> [[~~http~~://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC. The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint. May also be required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ.<ref>PMID:11336668</ref> <ref>PMID:12055248</ref> <ref>PMID:11955432</ref> <ref>PMID:15071507</ref> <ref>PMID:15468306</ref> <ref>PMID:14744996</ref> <ref>PMID:15574326</ref> <ref>PMID:15574327</ref> <ref>PMID:15456891</ref> <ref>PMID:15811628</ref> <ref>PMID:15936993</ref>	+	[[https://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/DCR1C_HUMAN DCR1C_HUMAN]] Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC. The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint. May also be required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ.<ref>PMID:11336668</ref> <ref>PMID:12055248</ref> <ref>PMID:11955432</ref> <ref>PMID:15071507</ref> <ref>PMID:15468306</ref> <ref>PMID:14744996</ref> <ref>PMID:15574326</ref> <ref>PMID:15574327</ref> <ref>PMID:15456891</ref> <ref>PMID:15811628</ref> <ref>PMID:15936993</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 25:

	==See Also==		==See Also==
-	*[[DNA ligase\|DNA ligase]]	+	*[[DNA ligase 3D structures\|DNA ligase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 31:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Blundell, T L]]		[[Category: Blundell, T L]]
	[[Category: Ochi, T]]		[[Category: Ochi, T]]

OCA at 08:25, 5 August 2016

2016-08-05T08:25:38Z

←Older revision		Revision as of 08:25, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of Human DNA ligase IV-Artemis Complex (Native)==		==Crystal Structure of Human DNA ligase IV-Artemis Complex (Native)==
	<StructureSection load='3w1g' size='340' side='right' caption='[[3w1g]], [[Resolution\|resolution]] 2.55Å' scene=''>		<StructureSection load='3w1g' size='340' side='right' caption='[[3w1g]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3w1g]] 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=3W1G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1G FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3w1g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W1G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1G FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3w1b\|3w1b]], [[3vnn\|3vnn]], [[1ik9\|1ik9]], [[3ii6\|3ii6]], [[2e2w\|2e2w]], [[1x9n\|1x9n]], [[3w5o\|3w5o]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3w1b\|3w1b]], [[3vnn\|3vnn]], [[1ik9\|1ik9]], [[3ii6\|3ii6]], [[2e2w\|2e2w]], [[1x9n\|1x9n]], [[3w5o\|3w5o]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LIG4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LIG4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3w1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w1g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w1g RCSB], [http://www.ebi.ac.uk/pdbsum/3w1g PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3w1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w1g OCA], [http://pdbe.org/3w1g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3w1g RCSB], [http://www.ebi.ac.uk/pdbsum/3w1g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3w1g ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3w1g" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Blundell, T L]]		[[Category: Blundell, T L]]
	[[Category: Ochi, T]]		[[Category: Ochi, T]]

OCA at 06:59, 21 December 2014

2014-12-21T06:59:50Z

←Older revision		Revision as of 06:59, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3w1g\| PDB=3w1g \| SCENE= }}~~	+	==Crystal Structure of Human DNA ligase IV-Artemis Complex (Native)==
-	===Crystal Structure of Human DNA ligase IV-Artemis Complex (Native)===	+	<StructureSection load='3w1g' size='340' side='right' caption='[[3w1g]], [[Resolution\|resolution]] 2.55Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23523427}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3w1g]] 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=3W1G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W1G FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3w1b\|3w1b]], [[3vnn\|3vnn]], [[1ik9\|1ik9]], [[3ii6\|3ii6]], [[2e2w\|2e2w]], [[1x9n\|1x9n]], [[3w5o\|3w5o]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LIG4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3w1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w1g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w1g RCSB], [http://www.ebi.ac.uk/pdbsum/3w1g PDBsum]</span></td></tr>
		+	</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. [[http://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Severe combined immunodeficiency, alymphocytotic type;Omenn syndrome. Defects in DCLRE1C 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.<ref>PMID:11336668</ref> <ref>PMID:12406895</ref> <ref>PMID:12921762</ref> <ref>PMID:12592555</ref> <ref>PMID:12569164</ref> Defects in DCLRE1C are the cause of severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:[http://omim.org/entry/602450 602450]]. SCIDA is a variety of RS-SCID caused by a founder mutation in Athabascan-speaking native Americans, being inherited as an autosomal recessive trait with an estimated gene frequency of 2.1% in the Navajo population. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID.<ref>PMID:12055248</ref> Defects in DCLRE1C are a cause of Omenn syndrome (OS) [MIM:[http://omim.org/entry/603554 603554]]. OS is characterized by severe combined immunodeficiency associated with erythrodermia, hepatosplenomegaly, lymphadenopathy and alopecia. Affected individuals have elevated T-lymphocyte counts with a restricted T-cell receptor (TCR) repertoire. They also generally lack B-lymphocytes, but have normal natural killer (NK) cell function (T+ B- NK+).		[[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. [[http://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Severe combined immunodeficiency, alymphocytotic type;Omenn syndrome. Defects in DCLRE1C 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.<ref>PMID:11336668</ref> <ref>PMID:12406895</ref> <ref>PMID:12921762</ref> <ref>PMID:12592555</ref> <ref>PMID:12569164</ref> Defects in DCLRE1C are the cause of severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:[http://omim.org/entry/602450 602450]]. SCIDA is a variety of RS-SCID caused by a founder mutation in Athabascan-speaking native Americans, being inherited as an autosomal recessive trait with an estimated gene frequency of 2.1% in the Navajo population. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID.<ref>PMID:12055248</ref> Defects in DCLRE1C are a cause of Omenn syndrome (OS) [MIM:[http://omim.org/entry/603554 603554]]. OS is characterized by severe combined immunodeficiency associated with erythrodermia, hepatosplenomegaly, lymphadenopathy and alopecia. Affected individuals have elevated T-lymphocyte counts with a restricted T-cell receptor (TCR) repertoire. They also generally lack B-lymphocytes, but have normal natural killer (NK) cell function (T+ B- NK+).
		+	== Function ==
		+	[[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> [[http://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC. The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint. May also be required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ.<ref>PMID:11336668</ref> <ref>PMID:12055248</ref> <ref>PMID:11955432</ref> <ref>PMID:15071507</ref> <ref>PMID:15468306</ref> <ref>PMID:14744996</ref> <ref>PMID:15574326</ref> <ref>PMID:15574327</ref> <ref>PMID:15456891</ref> <ref>PMID:15811628</ref> <ref>PMID:15936993</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Nonhomologous end joining (NHEJ) is central to the repair of double-stranded DNA breaks throughout the cell cycle and plays roles in the development of the immune system. Although three-dimensional structures of most components of NHEJ have been defined, those of the catalytic region of DNA ligase IV (LigIV), a specialized DNA ligase known to work in NHEJ, and of Artemis have remained unresolved. Here, we report the crystal structure at 2.4 A resolution of the catalytic region of LigIV (residues 1-609) in complex with an Artemis peptide. We describe interactions of the DNA-binding domain of LigIV with the continuous epitope of Artemis, which, together, form a three-helix bundle. A kink in the first helix of LigIV introduced by a conserved VPF motif gives rise to a hydrophobic pocket, which accommodates a conserved tryptophan from Artemis. We provide structural insights into features of LigIV among human DNA ligases.

-	~~==Function==~~	+	Structure of the catalytic region of DNA ligase IV in complex with an artemis fragment sheds light on double-strand break repair.,Ochi T, Gu X, Blundell TL Structure. 2013 Apr 2;21(4):672-9. doi: 10.1016/j.str.2013.02.014. Epub 2013 Mar , 21. PMID:23523427<ref>PMID:23523427</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> [[http://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T~~-cell receptor proteins are assembled from individual V~~, ~~(D)~~, ~~and J gene segments~~. V(~~D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs~~). ~~These DSBs present two types of DNA end structures~~: ~~hairpin sealed coding ends and phosphorylated blunt signal ends~~. ~~These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively~~. ~~This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC~~. ~~The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint~~. ~~May also be required for the repair of complex DSBs induced by ionizing radiation~~, ~~which require substantial end-processing prior to religation by NHEJ~~.~~<ref>~~PMID:11336668</ref> <ref>PMID:12055248</ref> <ref>PMID:11955432</ref> <ref>PMID:15071507</ref> <ref>PMID:15468306</ref> <ref>PMID:14744996</ref> <ref>PMID:15574326</ref> <ref>PMID:15574327</ref> <ref>PMID:15456891</ref> <ref>PMID:15811628</ref> <ref>PMID:~~15936993~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[3w1g]] 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=3W1G OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023523427</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[DNA ligase\|DNA ligase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Blundell, T L.]]	+	[[Category: Blundell, T L]]
-	[[Category: Ochi, T.]]	+	[[Category: Ochi, T]]
	[[Category: Dna ligase]]		[[Category: Dna ligase]]
	[[Category: Dna repair]]		[[Category: Dna repair]]

OCA at 06:35, 14 August 2013

2013-08-14T06:35:19Z

←Older revision		Revision as of 06:35, 14 August 2013
Line 1:		Line 1:
	{{STRUCTURE_3w1g\| PDB=3w1g \| SCENE= }}		{{STRUCTURE_3w1g\| PDB=3w1g \| SCENE= }}
	===Crystal Structure of Human DNA ligase IV-Artemis Complex (Native)===		===Crystal Structure of Human DNA ligase IV-Artemis Complex (Native)===
		+	{{ABSTRACT_PUBMED_23523427}}

	==Disease==		==Disease==
Line 12:		Line 13:

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:023523427</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Blundell, T L.]]		[[Category: Blundell, T L.]]

OCA at 01:41, 4 April 2013

2013-04-04T01:41:45Z

←Older revision		Revision as of 01:41, 4 April 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_3w1g\| PDB=3w1g \| SCENE= }}
		+	===Crystal Structure of Human DNA ligase IV-Artemis Complex (Native)===

-	The entry ~~3w1g~~ is ~~ON HOLD until Paper Publication~~	+	==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. [[http://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Severe combined immunodeficiency, alymphocytotic type;Omenn syndrome. Defects in DCLRE1C 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.<ref>PMID:11336668</ref> <ref>PMID:12406895</ref> <ref>PMID:12921762</ref> <ref>PMID:12592555</ref> <ref>PMID:12569164</ref> Defects in DCLRE1C are the cause of severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:[http://omim.org/entry/602450 602450]]. SCIDA is a variety of RS-SCID caused by a founder mutation in Athabascan-speaking native Americans, being inherited as an autosomal recessive trait with an estimated gene frequency of 2.1% in the Navajo population. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID.<ref>PMID:12055248</ref> Defects in DCLRE1C are a cause of Omenn syndrome (OS) [MIM:[http://omim.org/entry/603554 603554]]. OS is characterized by severe combined immunodeficiency associated with erythrodermia, hepatosplenomegaly, lymphadenopathy and alopecia. Affected individuals have elevated T-lymphocyte counts with a restricted T-cell receptor (TCR) repertoire. They also generally lack B-lymphocytes, but have normal natural killer (NK) cell function (T+ B- NK+).

-	~~Authors~~: ~~Ochi~~, T, ~~Blundell~~, T.L.	+	==Function==
		+	[[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> [[http://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC. The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint. May also be required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ.<ref>PMID:11336668</ref> <ref>PMID:12055248</ref> <ref>PMID:11955432</ref> <ref>PMID:15071507</ref> <ref>PMID:15468306</ref> <ref>PMID:14744996</ref> <ref>PMID:15574326</ref> <ref>PMID:15574327</ref> <ref>PMID:15456891</ref> <ref>PMID:15811628</ref> <ref>PMID:15936993</ref>

-	~~Description: Crystal~~ Structure ~~of Human DNA ligase IV~~-~~Artemis Complex (Native)~~	+	==About this Structure==
		+	[[3w1g]] 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=3W1G OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Blundell, T L.]]
		+	[[Category: Ochi, T.]]
		+	[[Category: Dna ligase]]
		+	[[Category: Dna repair]]
		+	[[Category: Ligase]]
		+	[[Category: Non homologous end joining]]
		+	[[Category: Xrcc4]]

OCA at 20:33, 12 December 2012

2012-12-12T20:33:40Z

←Older revision		Revision as of 20:33, 12 December 2012
Line 5:		Line 5:
	Authors: Ochi, T, Blundell, T.L.		Authors: Ochi, T, Blundell, T.L.

-	Description: Crystal Structure of Human DNA ligase IV Artemis Complex (Native)	+	Description: Crystal Structure of Human DNA ligase IV-Artemis Complex (Native)

OCA at 10:17, 5 December 2012

2012-12-05T10:17:16Z

←Older revision		Revision as of 10:17, 5 December 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3w1g is ON HOLD	+	The entry 3w1g is ON HOLD until Paper Publication

	Authors: Ochi, T, Blundell, T.L.		Authors: Ochi, T, Blundell, T.L.

	Description: Crystal Structure of Human DNA ligase IV Artemis Complex (Native)		Description: Crystal Structure of Human DNA ligase IV Artemis Complex (Native)

OCA at 13:50, 28 November 2012

2012-11-28T13:50:33Z

←Older revision		Revision as of 13:50, 28 November 2012
Line 3:		Line 3:
	The entry 3w1g is ON HOLD		The entry 3w1g is ON HOLD

-	Authors: Ochi, T, Blundell, T. L.	+	Authors: Ochi, T, Blundell, T.L.

	Description: Crystal Structure of Human DNA ligase IV Artemis Complex (Native)		Description: Crystal Structure of Human DNA ligase IV Artemis Complex (Native)

OCA: Protected "3w1g" [edit=sysop:move=sysop]

2012-11-21T08:52:49Z

Protected "3w1g" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:52, 21 November 2012