6cim - Revision history

OCA at 15:05, 4 October 2023

OCA — Wed, 04 Oct 2023 15:05:35 GMT

←Older revision		Revision as of 15:05, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='6cim' size='340' side='right'caption='[[6cim]], [[Resolution\|resolution]] 3.60Å' scene=''>		<StructureSection load='6cim' size='340' side='right'caption='[[6cim]], [[Resolution\|resolution]] 3.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cim]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~] and [https://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CIM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cim]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CIM FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>~~, ~~<scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 3.6Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max-height: 3em;~~'>~~[[6cik\|6cik]], [[6cil\|6cil]], [[5zdz\|5zdz]], [[5ze0\|5ze0]], [[5ze1\|5ze1]], [[5ze2\|5ze2]], [[6cg0\|6cg0]], [[6cij\|6cij]], [[4wwx\|4wwx]]~~</~~div~~><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b~~></td><td class="sblockDat">Rag1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Rag2, Rag-2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), HMGB1, HMG1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6cim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cim OCA], [https://pdbe.org/6cim PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cim RCSB], [https://www.ebi.ac.uk/pdbsum/6cim PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cim 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=6cim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cim OCA], [https://pdbe.org/6cim PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cim RCSB], [https://www.ebi.ac.uk/pdbsum/6cim PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cim ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/HMGB1_HUMAN HMGB1_HUMAN]] DNA binding proteins that associates with chromatin and has the ability to bend DNA. Binds preferentially single-stranded DNA. Involved in V(D)J recombination by acting as a cofactor of the RAG complex. Acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS). Heparin-binding protein that has a role in the extension of neurite-type cytoplasmic processes in developing cells (By similarity). [[https://www.uniprot.org/uniprot/RAG2_MOUSE RAG2_MOUSE]] Core component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. DNA cleavage by the RAG complex occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3.<ref>PMID:2360047</ref> <ref>PMID:8521468</ref> <ref>PMID:9094713</ref> <ref>PMID:16111638</ref> <ref>PMID:19524534</ref> <ref>PMID:19448632</ref> [[https://www.uniprot.org/uniprot/RAG1_MOUSE RAG1_MOUSE]] Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as a E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1.<ref>PMID:2598259</ref> <ref>PMID:8521468</ref> <ref>PMID:9094713</ref> <ref>PMID:10601032</ref> <ref>PMID:10678172</ref> <ref>PMID:12629039</ref> <ref>PMID:14671314</ref> <ref>PMID:17028591</ref> <ref>PMID:19524534</ref> <ref>PMID:19118899</ref> <ref>PMID:19448632</ref> <ref>PMID:20122409</ref> <ref>PMID:19396172</ref>	+	[https://www.uniprot.org/uniprot/RAG1_MOUSE RAG1_MOUSE] Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as a E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1.<ref>PMID:2598259</ref> <ref>PMID:8521468</ref> <ref>PMID:9094713</ref> <ref>PMID:10601032</ref> <ref>PMID:10678172</ref> <ref>PMID:12629039</ref> <ref>PMID:14671314</ref> <ref>PMID:17028591</ref> <ref>PMID:19524534</ref> <ref>PMID:19118899</ref> <ref>PMID:19448632</ref> <ref>PMID:20122409</ref> <ref>PMID:19396172</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Chen, X]]	+	[[Category: Chen X]]
-	[[Category: Chuenchor, W]]	+	[[Category: Chuenchor W]]
-	[[Category: Gellert, M]]	+	[[Category: Gellert M]]
-	[[Category: Kim~~, M S~~]]	+	[[Category: Kim MS]]
-	[[Category: Yang, W]]	+	[[Category: Yang W]]
-	~~[[Category: Rag1/2]]~~	+
-	~~[[Category: Recombination]]~~	+
-	~~[[Category: Recombination-dna complex]]~~	+
-	~~[[Category: Rss]]~~	+
-	~~[[Category: Vdj recombination~~]]	+

OCA at 11:41, 23 March 2022

OCA — Wed, 23 Mar 2022 11:41:19 GMT

←Older revision		Revision as of 11:41, 23 March 2022
Line 3:		Line 3:
	<StructureSection load='6cim' size='340' side='right'caption='[[6cim]], [[Resolution\|resolution]] 3.60Å' scene=''>		<StructureSection load='6cim' size='340' side='right'caption='[[6cim]], [[Resolution\|resolution]] 3.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cim]] is a 10 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human] and [~~http~~://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6CIM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cim]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CIM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6cik\|6cik]], [[6cil\|6cil]], [[5zdz\|5zdz]], [[5ze0\|5ze0]], [[5ze1\|5ze1]], [[5ze2\|5ze2]], [[6cg0\|6cg0]], [[6cij\|6cij]], [[4wwx\|4wwx]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6cik\|6cik]], [[6cil\|6cil]], [[5zdz\|5zdz]], [[5ze0\|5ze0]], [[5ze1\|5ze1]], [[5ze2\|5ze2]], [[6cg0\|6cg0]], [[6cij\|6cij]], [[4wwx\|4wwx]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Rag1 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Rag2, Rag-2 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), HMGB1, HMG1 ([~~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">Rag1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Rag2, Rag-2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), HMGB1, HMG1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6cim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cim OCA], [~~http~~://pdbe.org/6cim PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6cim RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6cim PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6cim 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=6cim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cim OCA], [https://pdbe.org/6cim PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cim RCSB], [https://www.ebi.ac.uk/pdbsum/6cim PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cim ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/HMGB1_HUMAN HMGB1_HUMAN]] DNA binding proteins that associates with chromatin and has the ability to bend DNA. Binds preferentially single-stranded DNA. Involved in V(D)J recombination by acting as a cofactor of the RAG complex. Acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS). Heparin-binding protein that has a role in the extension of neurite-type cytoplasmic processes in developing cells (By similarity). [[~~http~~://www.uniprot.org/uniprot/RAG2_MOUSE RAG2_MOUSE]] Core component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. DNA cleavage by the RAG complex occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3.<ref>PMID:2360047</ref> <ref>PMID:8521468</ref> <ref>PMID:9094713</ref> <ref>PMID:16111638</ref> <ref>PMID:19524534</ref> <ref>PMID:19448632</ref> [[~~http~~://www.uniprot.org/uniprot/RAG1_MOUSE RAG1_MOUSE]] Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as a E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1.<ref>PMID:2598259</ref> <ref>PMID:8521468</ref> <ref>PMID:9094713</ref> <ref>PMID:10601032</ref> <ref>PMID:10678172</ref> <ref>PMID:12629039</ref> <ref>PMID:14671314</ref> <ref>PMID:17028591</ref> <ref>PMID:19524534</ref> <ref>PMID:19118899</ref> <ref>PMID:19448632</ref> <ref>PMID:20122409</ref> <ref>PMID:19396172</ref>	+	[[https://www.uniprot.org/uniprot/HMGB1_HUMAN HMGB1_HUMAN]] DNA binding proteins that associates with chromatin and has the ability to bend DNA. Binds preferentially single-stranded DNA. Involved in V(D)J recombination by acting as a cofactor of the RAG complex. Acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS). Heparin-binding protein that has a role in the extension of neurite-type cytoplasmic processes in developing cells (By similarity). [[https://www.uniprot.org/uniprot/RAG2_MOUSE RAG2_MOUSE]] Core component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. DNA cleavage by the RAG complex occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3.<ref>PMID:2360047</ref> <ref>PMID:8521468</ref> <ref>PMID:9094713</ref> <ref>PMID:16111638</ref> <ref>PMID:19524534</ref> <ref>PMID:19448632</ref> [[https://www.uniprot.org/uniprot/RAG1_MOUSE RAG1_MOUSE]] Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as a E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1.<ref>PMID:2598259</ref> <ref>PMID:8521468</ref> <ref>PMID:9094713</ref> <ref>PMID:10601032</ref> <ref>PMID:10678172</ref> <ref>PMID:12629039</ref> <ref>PMID:14671314</ref> <ref>PMID:17028591</ref> <ref>PMID:19524534</ref> <ref>PMID:19118899</ref> <ref>PMID:19448632</ref> <ref>PMID:20122409</ref> <ref>PMID:19396172</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 12:50, 25 December 2019

OCA — Wed, 25 Dec 2019 12:50:43 GMT

←Older revision		Revision as of 12:50, 25 December 2019
Line 1:		Line 1:

	==Pre-Reaction Complex, RAG1(E962Q)/2-nicked/intact 12/23RSS complex in Mn2+==		==Pre-Reaction Complex, RAG1(E962Q)/2-nicked/intact 12/23RSS complex in Mn2+==
-	<StructureSection load='6cim' size='340' side='right' caption='[[6cim]], [[Resolution\|resolution]] 3.60Å' scene=''>	+	<StructureSection load='6cim' size='340' side='right'caption='[[6cim]], [[Resolution\|resolution]] 3.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6cim]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CIM FirstGlance]. <br>		<table><tr><td colspan='2'>[[6cim]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CIM FirstGlance]. <br>
Line 23:		Line 23:
	==See Also==		==See Also==
	*[[High mobility group protein\|High mobility group protein]]		*[[High mobility group protein\|High mobility group protein]]
-	*[[Recombination-activating gene\|Recombination-activating gene]]	+	*[[Recombination-activating gene 3D structures\|Recombination-activating gene 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Lk3 transgenic mice]]		[[Category: Lk3 transgenic mice]]
	[[Category: Chen, X]]		[[Category: Chen, X]]

OCA at 08:27, 21 February 2019

OCA — Thu, 21 Feb 2019 08:27:07 GMT

←Older revision		Revision as of 08:27, 21 February 2019
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 6cim" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6cim" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[High mobility group protein\|High mobility group protein]]
		+	*[[Recombination-activating gene\|Recombination-activating gene]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:33, 2 May 2018

OCA — Wed, 02 May 2018 08:33:50 GMT

←Older revision		Revision as of 08:33, 2 May 2018
Line 3:		Line 3:
	<StructureSection load='6cim' size='340' side='right' caption='[[6cim]], [[Resolution\|resolution]] 3.60Å' scene=''>		<StructureSection load='6cim' size='340' side='right' caption='[[6cim]], [[Resolution\|resolution]] 3.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cim]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CIM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cim]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CIM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6cik\|6cik]], [[6cil\|6cil]], [[5zdz\|5zdz]], [[5ze0\|5ze0]], [[5ze1\|5ze1]], [[5ze2\|5ze2]], [[6cg0\|6cg0]], [[6cij\|6cij]], [[4wwx\|4wwx]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6cik\|6cik]], [[6cil\|6cil]], [[5zdz\|5zdz]], [[5ze0\|5ze0]], [[5ze1\|5ze1]], [[5ze2\|5ze2]], [[6cg0\|6cg0]], [[6cij\|6cij]], [[4wwx\|4wwx]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Rag1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Rag2, Rag-2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), HMGB1, HMG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6cim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cim OCA], [http://pdbe.org/6cim PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cim RCSB], [http://www.ebi.ac.uk/pdbsum/6cim PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cim ProSAT]</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=6cim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cim OCA], [http://pdbe.org/6cim PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cim RCSB], [http://www.ebi.ac.uk/pdbsum/6cim PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cim ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Chen, X]]		[[Category: Chen, X]]
	[[Category: Chuenchor, W]]		[[Category: Chuenchor, W]]

OCA at 05:35, 25 April 2018

OCA — Wed, 25 Apr 2018 05:35:42 GMT

←Older revision		Revision as of 05:35, 25 April 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6cim is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Pre-Reaction Complex, RAG1(E962Q)/2-nicked/intact 12/23RSS complex in Mn2+==
		+	<StructureSection load='6cim' size='340' side='right' caption='[[6cim]], [[Resolution\|resolution]] 3.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6cim]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CIM FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6cik\|6cik]], [[6cil\|6cil]], [[5zdz\|5zdz]], [[5ze0\|5ze0]], [[5ze1\|5ze1]], [[5ze2\|5ze2]], [[6cg0\|6cg0]], [[6cij\|6cij]], [[4wwx\|4wwx]]</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=6cim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cim OCA], [http://pdbe.org/6cim PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cim RCSB], [http://www.ebi.ac.uk/pdbsum/6cim PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cim ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/HMGB1_HUMAN HMGB1_HUMAN]] DNA binding proteins that associates with chromatin and has the ability to bend DNA. Binds preferentially single-stranded DNA. Involved in V(D)J recombination by acting as a cofactor of the RAG complex. Acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS). Heparin-binding protein that has a role in the extension of neurite-type cytoplasmic processes in developing cells (By similarity). [[http://www.uniprot.org/uniprot/RAG2_MOUSE RAG2_MOUSE]] Core component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. DNA cleavage by the RAG complex occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3.<ref>PMID:2360047</ref> <ref>PMID:8521468</ref> <ref>PMID:9094713</ref> <ref>PMID:16111638</ref> <ref>PMID:19524534</ref> <ref>PMID:19448632</ref> [[http://www.uniprot.org/uniprot/RAG1_MOUSE RAG1_MOUSE]] Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as a E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1.<ref>PMID:2598259</ref> <ref>PMID:8521468</ref> <ref>PMID:9094713</ref> <ref>PMID:10601032</ref> <ref>PMID:10678172</ref> <ref>PMID:12629039</ref> <ref>PMID:14671314</ref> <ref>PMID:17028591</ref> <ref>PMID:19524534</ref> <ref>PMID:19118899</ref> <ref>PMID:19448632</ref> <ref>PMID:20122409</ref> <ref>PMID:19396172</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	To initiate V(D)J recombination for generating the adaptive immune response of vertebrates, RAG1/2 recombinase cleaves DNA at a pair of recombination signal sequences, the 12- and 23-RSS. We have determined crystal and cryo-EM structures of RAG1/2 with DNA in the pre-reaction and hairpin-forming complexes up to 2.75 A resolution. Both protein and DNA exhibit structural plasticity and undergo dramatic conformational changes. Coding-flank DNAs extensively rotate, shift, and deform for nicking and hairpin formation. Two intertwined RAG1 subunits crisscross four times between the asymmetric pair of severely bent 12/23-RSS DNAs. Location-sensitive bending of 60 degrees and 150 degrees in 12- and 23-RSS spacers, respectively, must occur for RAG1/2 to capture the nonamers and pair the heptamers for symmetric double-strand breakage. DNA pairing is thus sequence-context dependent and structure specific, which partly explains the "beyond 12/23" restriction. Finally, catalysis in crystallo reveals the process of DNA hairpin formation and its stabilization by interleaved base stacking.

-	~~Authors: Chuenchor~~, W., Chen, X., ~~Kim~~, ~~M.S.~~, ~~Gellert~~, M., Yang, W.	+	Cracking the DNA Code for V(D)J Recombination.,Kim MS, Chuenchor W, Chen X, Cui Y, Zhang X, Zhou ZH, Gellert M, Yang W Mol Cell. 2018 Apr 19;70(2):358-370.e4. doi: 10.1016/j.molcel.2018.03.008. Epub, 2018 Apr 5. PMID:29628308<ref>PMID:29628308</ref>

-	~~Description: Pre-Reaction Complex~~, ~~RAG1(E962Q)~~/2-~~nicked~~/~~intact 12~~/~~23RSS complex in Mn2+~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category: Kim, M.S]]~~	+	<div class="pdbe-citations 6cim" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Chen, X]]		[[Category: Chen, X]]
-	[[Category: Gellert, M]]
	[[Category: Chuenchor, W]]		[[Category: Chuenchor, W]]
		+	[[Category: Gellert, M]]
		+	[[Category: Kim, M S]]
	[[Category: Yang, W]]		[[Category: Yang, W]]
		+	[[Category: Rag1/2]]
		+	[[Category: Recombination]]
		+	[[Category: Recombination-dna complex]]
		+	[[Category: Rss]]
		+	[[Category: Vdj recombination]]

OCA: Protected "6cim" [edit=sysop:move=sysop]

OCA — Thu, 08 Mar 2018 03:46:28 GMT

Protected "6cim" [edit=sysop:move=sysop]

←Older revision

Revision as of 03:46, 8 March 2018

OCA: New page: '''Unreleased structure''' The entry 6cim is ON HOLD until Paper Publication Authors: Chuenchor, W., Chen, X., Kim, M.S., Gellert, M., Yang, W. Description: Pre-Reaction Complex, RAG1(...

OCA — Thu, 08 Mar 2018 03:46:27 GMT

New page: '''Unreleased structure''' The entry 6cim is ON HOLD until Paper Publication Authors: Chuenchor, W., Chen, X., Kim, M.S., Gellert, M., Yang, W. Description: Pre-Reaction Complex, RAG1(...

New page

'''Unreleased structure'''

The entry 6cim is ON HOLD until Paper Publication

Authors: Chuenchor, W., Chen, X., Kim, M.S., Gellert, M., Yang, W.

Description: Pre-Reaction Complex, RAG1(E962Q)/2-nicked/intact 12/23RSS complex in Mn2+
[[Category: Unreleased Structures]]
[[Category: Kim, M.S]]
[[Category: Chen, X]]
[[Category: Gellert, M]]
[[Category: Chuenchor, W]]
[[Category: Yang, W]]