6oes - Revision history

OCA at 09:23, 20 March 2024

OCA — Wed, 20 Mar 2024 09:23:53 GMT

←Older revision		Revision as of 09:23, 20 March 2024
Line 3:		Line 3:
	<SX load='6oes' size='340' side='right' viewer='molstar' caption='[[6oes]], [[Resolution\|resolution]] 3.06Å' scene=''>		<SX load='6oes' size='340' side='right' viewer='molstar' caption='[[6oes]], [[Resolution\|resolution]] 3.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6oes]] is a 10 chain structure with sequence from [~~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=6OES OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6OES FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6oes]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] 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=6OES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OES FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CA:CALCIUM+ION'>CA</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">Electron Microscopy, [[Resolution\|Resolution]] 3.06Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[6oem\|6oem]], [[6oen\|6oen]], [[6oeo\|6oeo]], [[6oep\|6oep]], [[6oeq\|6oeq]], [[6oer\|6oer]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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 ([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])~~</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=6oes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oes OCA], [https://pdbe.org/6oes PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oes RCSB], [https://www.ebi.ac.uk/pdbsum/6oes PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oes ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6oes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oes OCA], [~~http~~://pdbe.org/6oes PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6oes RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6oes PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6oes ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[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> [[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>	+	[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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The RAG1-RAG2 recombinase (RAG) cleaves DNA to initiate V(D)J recombination, but RAG also belongs to the RNH-type transposase family. To learn how RAG-catalyzed transposition is inhibited in developing lymphocytes, we determined the structure of a DNA-strand transfer complex of mouse RAG at 3.1-A resolution. The target DNA is a T form (T for transpositional target), which contains two >80 degrees kinks towards the minor groove, only 3 bp apart. RAG2, a late evolutionary addition in V(D)J recombination, appears to enforce the sharp kinks and additional inter-segment twisting in target DNA and thus attenuates unwanted transposition. In contrast to strand transfer complexes of genuine transposases, where severe kinks occur at the integration sites of target DNA and thus prevent the reverse reaction, the sharp kink with RAG is 1 bp away from the integration site. As a result, RAG efficiently catalyzes the disintegration reaction that restores the RSS (donor) and target DNA.	+
-		+
-	How mouse RAG recombinase avoids DNA transposition.,Chen X, Cui Y, Wang H, Zhou ZH, Gellert M, Yang W Nat Struct Mol Biol. 2020 Feb;27(2):127-133. doi: 10.1038/s41594-019-0366-z. Epub, 2020 Feb 3. PMID:32015553<ref>PMID:32015553</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6oes" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</SX>		</SX>
		+	[[Category: Escherichia coli K-12]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Chen, X]]	+	[[Category: Chen X]]
-	[[Category: Cui, Y]]	+	[[Category: Cui Y]]
-	[[Category: Gellert, M]]	+	[[Category: Gellert M]]
-	[[Category: Yang, W]]	+	[[Category: Yang W]]
-	[[Category: Zhou~~, Z H]]~~	+	[[Category: Zhou ZH]]
-	~~[[Category: Dna transposition]]~~	+
-	~~[[Category: Rag]]~~	+
-	~~[[Category: Recombination]]~~	+
-	~~[[Category: Recombination-dna complex]]~~	+
-	~~[[Category: Scid~~]]	+

OCA at 05:46, 5 August 2020

OCA — Wed, 05 Aug 2020 05:46:49 GMT

←Older revision		Revision as of 05:46, 5 August 2020
Line 3:		Line 3:
	<SX load='6oes' size='340' side='right' viewer='molstar' caption='[[6oes]], [[Resolution\|resolution]] 3.06Å' scene=''>		<SX load='6oes' size='340' side='right' viewer='molstar' caption='[[6oes]], [[Resolution\|resolution]] 3.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6oes]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OES OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OES FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6oes]] is a 10 chain structure with sequence from [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=6OES OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OES FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=CA:CALCIUM+ION'>CA</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">[[6oem\|6oem]], [[6oen\|6oen]], [[6oeo\|6oeo]], [[6oep\|6oep]], [[6oeq\|6oeq]], [[6oer\|6oer]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6oem\|6oem]], [[6oen\|6oen]], [[6oeo\|6oeo]], [[6oep\|6oep]], [[6oeq\|6oeq]], [[6oer\|6oer]]</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])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6oes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oes OCA], [http://pdbe.org/6oes PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oes RCSB], [http://www.ebi.ac.uk/pdbsum/6oes PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oes ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6oes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oes OCA], [http://pdbe.org/6oes PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oes RCSB], [http://www.ebi.ac.uk/pdbsum/6oes PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oes ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[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> [[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> [[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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The RAG1-RAG2 recombinase (RAG) cleaves DNA to initiate V(D)J recombination, but RAG also belongs to the RNH-type transposase family. To learn how RAG-catalyzed transposition is inhibited in developing lymphocytes, we determined the structure of a DNA-strand transfer complex of mouse RAG at 3.1-A resolution. The target DNA is a T form (T for transpositional target), which contains two >80 degrees kinks towards the minor groove, only 3 bp apart. RAG2, a late evolutionary addition in V(D)J recombination, appears to enforce the sharp kinks and additional inter-segment twisting in target DNA and thus attenuates unwanted transposition. In contrast to strand transfer complexes of genuine transposases, where severe kinks occur at the integration sites of target DNA and thus prevent the reverse reaction, the sharp kink with RAG is 1 bp away from the integration site. As a result, RAG efficiently catalyzes the disintegration reaction that restores the RSS (donor) and target DNA.
		+
		+	How mouse RAG recombinase avoids DNA transposition.,Chen X, Cui Y, Wang H, Zhou ZH, Gellert M, Yang W Nat Struct Mol Biol. 2020 Feb;27(2):127-133. doi: 10.1038/s41594-019-0366-z. Epub, 2020 Feb 3. PMID:32015553<ref>PMID:32015553</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6oes" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
Line 15:		Line 25:
	</SX>		</SX>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Chen, X]]		[[Category: Chen, X]]
	[[Category: Cui, Y]]		[[Category: Cui, Y]]

OCA at 03:54, 11 April 2020

OCA — Sat, 11 Apr 2020 03:54:44 GMT

←Older revision		Revision as of 03:54, 11 April 2020
Line 3:		Line 3:
	<SX load='6oes' size='340' side='right' viewer='molstar' caption='[[6oes]], [[Resolution\|resolution]] 3.06Å' scene=''>		<SX load='6oes' size='340' side='right' viewer='molstar' caption='[[6oes]], [[Resolution\|resolution]] 3.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6oes]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OES OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6OES FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6oes]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OES OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OES FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=CA:CALCIUM+ION'>CA</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">[[6oem\|6oem]], [[6oen\|6oen]], [[6oeo\|6oeo]], [[6oep\|6oep]], [[6oeq\|6oeq]], [[6oer\|6oer]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6oem\|6oem]], [[6oen\|6oen]], [[6oeo\|6oeo]], [[6oep\|6oep]], [[6oeq\|6oeq]], [[6oer\|6oer]]</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=6oes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oes OCA], [http://pdbe.org/6oes PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oes RCSB], [http://www.ebi.ac.uk/pdbsum/6oes PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oes ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6oes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oes OCA], [http://pdbe.org/6oes PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oes RCSB], [http://www.ebi.ac.uk/pdbsum/6oes PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oes ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 23:10, 6 March 2020

OCA — Fri, 06 Mar 2020 23:10:39 GMT

←Older revision		Revision as of 23:10, 6 March 2020
Line 1:		Line 1:

	==Cryo-EM structure of mouse RAG1/2 STC complex (without NBD domain)==		==Cryo-EM structure of mouse RAG1/2 STC complex (without NBD domain)==
-	<~~StructureSection~~ load='6oes' size='340' side='right'caption='[[6oes]], [[Resolution\|resolution]] 3.06Å' scene=''>	+	<SX load='6oes' size='340' side='right' viewer='molstar' caption='[[6oes]], [[Resolution\|resolution]] 3.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6oes]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OES FirstGlance]. <br>		<table><tr><td colspan='2'>[[6oes]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OES FirstGlance]. <br>
Line 13:		Line 13:
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Chen, X]]		[[Category: Chen, X]]

OCA at 16:12, 22 January 2020

OCA — Wed, 22 Jan 2020 16:12:50 GMT

←Older revision		Revision as of 16:12, 22 January 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6oes is ~~ON HOLD until Paper Publication~~	+	==Cryo-EM structure of mouse RAG1/2 STC complex (without NBD domain)==
-		+	<StructureSection load='6oes' size='340' side='right'caption='[[6oes]], [[Resolution\|resolution]] 3.06Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6oes]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OES OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OES FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6oem\|6oem]], [[6oen\|6oen]], [[6oeo\|6oeo]], [[6oep\|6oep]], [[6oeq\|6oeq]], [[6oer\|6oer]]</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=6oes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oes OCA], [http://pdbe.org/6oes PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oes RCSB], [http://www.ebi.ac.uk/pdbsum/6oes PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oes ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[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> [[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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Chen, X]]
		+	[[Category: Cui, Y]]
		+	[[Category: Gellert, M]]
		+	[[Category: Yang, W]]
		+	[[Category: Zhou, Z H]]
		+	[[Category: Dna transposition]]
		+	[[Category: Rag]]
		+	[[Category: Recombination]]
		+	[[Category: Recombination-dna complex]]
		+	[[Category: Scid]]

OCA at 03:57, 12 June 2019

OCA — Wed, 12 Jun 2019 03:57:41 GMT

←Older revision		Revision as of 03:57, 12 June 2019
Line 3:		Line 3:
	The entry 6oes is ON HOLD until Paper Publication		The entry 6oes is ON HOLD until Paper Publication

-	Authors: ~~Chen, X., Cui, Y., Zhou, Z.H., Yang, W., Gellert, M.~~	+	Authors:

-	Description: ~~Cryo-EM structure of mouse RAG1/2 STC complex (without NBD domain)~~	+	Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Zhou, Z.H]]
-	[[Category: Cui, Y]]
-	[[Category: Chen, X]]
-	[[Category: Gellert, M]]
-	[[Category: Yang, W]]

OCA at 05:44, 21 May 2019

OCA — Tue, 21 May 2019 05:44:23 GMT

←Older revision		Revision as of 05:44, 21 May 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6oes is ON HOLD	+	The entry 6oes is ON HOLD until Paper Publication

	Authors: Chen, X., Cui, Y., Zhou, Z.H., Yang, W., Gellert, M.		Authors: Chen, X., Cui, Y., Zhou, Z.H., Yang, W., Gellert, M.

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

OCA — Wed, 03 Apr 2019 04:48:04 GMT

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

←Older revision

Revision as of 04:48, 3 April 2019

OCA: New page: '''Unreleased structure''' The entry 6oes is ON HOLD Authors: Chen, X., Cui, Y., Zhou, Z.H., Yang, W., Gellert, M. Description: Cryo-EM structure of mouse RAG1/2 STC complex (without N...

OCA — Wed, 03 Apr 2019 04:48:02 GMT

New page: '''Unreleased structure''' The entry 6oes is ON HOLD Authors: Chen, X., Cui, Y., Zhou, Z.H., Yang, W., Gellert, M. Description: Cryo-EM structure of mouse RAG1/2 STC complex (without N...

New page

'''Unreleased structure'''

The entry 6oes is ON HOLD

Authors: Chen, X., Cui, Y., Zhou, Z.H., Yang, W., Gellert, M.

Description: Cryo-EM structure of mouse RAG1/2 STC complex (without NBD domain)
[[Category: Unreleased Structures]]
[[Category: Zhou, Z.H]]
[[Category: Cui, Y]]
[[Category: Chen, X]]
[[Category: Gellert, M]]
[[Category: Yang, W]]