4dpg - Revision history

OCA at 10:54, 1 March 2024

2024-03-01T10:54:14Z

← Older revision		Revision as of 10:54, 1 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dpg]] is a 12 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=4DPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DPG FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dpg]] is a 12 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=4DPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DPG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.844Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=4dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpg OCA], [https://pdbe.org/4dpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dpg RCSB], [https://www.ebi.ac.uk/pdbsum/4dpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dpg 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=4dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpg OCA], [https://pdbe.org/4dpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dpg RCSB], [https://www.ebi.ac.uk/pdbsum/4dpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dpg ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/SYK_HUMAN SYK_HUMAN]] Defects in KARS are the cause of Charcot-Marie-Tooth disease recessive intermediate type B (CMTRIB) [MIM:[https://omim.org/entry/613641 613641]]; also called Charcot-Marie-Tooth neuropathy recessive intermediate B. CMTRIB is a form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.<ref>PMID:20920668</ref>		[https://www.uniprot.org/uniprot/SYK_HUMAN SYK_HUMAN] Defects in KARS are the cause of Charcot-Marie-Tooth disease recessive intermediate type B (CMTRIB) [MIM:[https://omim.org/entry/613641 613641]; also called Charcot-Marie-Tooth neuropathy recessive intermediate B. CMTRIB is a form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.<ref>PMID:20920668</ref>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/SYK_HUMAN SYK_HUMAN]] Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages. Catalyzes the synthesis of diadenosine oligophosphate (Ap4A), a signaling molecule involved in the activation of MITF transcriptional activity. Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation.<ref>PMID:5338216</ref> <ref>PMID:15851690</ref>		[https://www.uniprot.org/uniprot/SYK_HUMAN SYK_HUMAN] Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages. Catalyzes the synthesis of diadenosine oligophosphate (Ap4A), a signaling molecule involved in the activation of MITF transcriptional activity. Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation.<ref>PMID:5338216</ref> <ref>PMID:15851690</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Lysyl-tRNA synthetase (LysRS), a component of the translation apparatus, is released from the cytoplasmic multi-tRNA synthetase complex (MSC) to activate the transcription factor MITF in stimulated mast cells through undefined mechanisms. Here we show that Ser207 phosphorylation provokes a new conformer of LysRS that inactivates its translational function but activates its transcriptional function. The crystal structure of an MSC subcomplex established that LysRS is held in the MSC by binding to the N terminus of the scaffold protein p38/AIMP2. Phosphorylation-created steric clashes at the LysRS domain interface disrupt its binding grooves for p38/AIMP2, releasing LysRS and provoking its nuclear translocation. This alteration also exposes the C-terminal domain of LysRS to bind to MITF and triggers LysRS-directed production of the second messenger Ap(4)A that activates MITF. Thus our results establish that a single conformational change triggered by phosphorylation leads to multiple effects driving an exclusive switch of LysRS function from translation to transcription.

	Structural Switch of Lysyl-tRNA Synthetase between Translation and Transcription.,Ofir-Birin Y, Fang P, Bennett SP, Zhang HM, Wang J, Rachmin I, Shapiro R, Song J, Dagan A, Pozo J, Kim S, Marshall AG, Schimmel P, Yang XL, Nechushtan H, Razin E, Guo M Mol Cell. 2013 Jan 10;49(1):30-42. doi: 10.1016/j.molcel.2012.10.010. Epub 2012, Nov 15. PMID:23159739<ref>PMID:23159739</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4dpg" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==

OCA at 08:33, 21 September 2022

2022-09-21T08:33:09Z

← Older revision		Revision as of 08:33, 21 September 2022
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	==Crystal Structure of Human LysRS: P38/AIMP2 Complex I==		==Crystal Structure of Human LysRS: P38/AIMP2 Complex I==
	<StructureSection load='4dpg' size='340' side='right' caption='[[4dpg]], [[Resolution\|resolution]] 2.84Å' scene=''>		<StructureSection load='4dpg' size='340' side='right'caption='[[4dpg]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dpg]] is a 12 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=4DPG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4DPG FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dpg]] is a 12 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=4DPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DPG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene~~></td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dpj\|4dpj]]</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=4dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpg OCA], [https://pdbe.org/4dpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dpg RCSB], [https://www.ebi.ac.uk/pdbsum/4dpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dpg ProSAT]</span></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KARS, KIAA0070 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), AIMP2, JTV1, PRO0992 ([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/Lysine--tRNA_ligase Lysine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.6 6.1.1.6] </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=4dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpg OCA], [~~http~~://pdbe.org/4dpg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4dpg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4dpg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4dpg ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/SYK_HUMAN SYK_HUMAN]] Defects in KARS are the cause of Charcot-Marie-Tooth disease recessive intermediate type B (CMTRIB) [MIM:[~~http~~://omim.org/entry/613641 613641]]; also called Charcot-Marie-Tooth neuropathy recessive intermediate B. CMTRIB is a form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.<ref>PMID:20920668</ref>		[[https://www.uniprot.org/uniprot/SYK_HUMAN SYK_HUMAN]] Defects in KARS are the cause of Charcot-Marie-Tooth disease recessive intermediate type B (CMTRIB) [MIM:[https://omim.org/entry/613641 613641]]; also called Charcot-Marie-Tooth neuropathy recessive intermediate B. CMTRIB is a form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.<ref>PMID:20920668</ref>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/SYK_HUMAN SYK_HUMAN]] Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages. Catalyzes the synthesis of diadenosine oligophosphate (Ap4A), a signaling molecule involved in the activation of MITF transcriptional activity. Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation.<ref>PMID:5338216</ref> <ref>PMID:15851690</ref> [[http://www.uniprot.org/uniprot/AIMP2_HUMAN AIMP2_HUMAN]] Required for assembly and stability of the aminoacyl-tRNA synthase complex. Mediates ubiquitination and degradation of FUBP1, a transcriptional activator of MYC, leading to MYC down-regulation which is required for aveolar type II cell differentiation. Blocks MDM2-mediated ubiquitination and degradation of p53/TP53. Functions as a proapoptotic factor.<ref>PMID:16135753</ref>		[[https://www.uniprot.org/uniprot/SYK_HUMAN SYK_HUMAN]] Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages. Catalyzes the synthesis of diadenosine oligophosphate (Ap4A), a signaling molecule involved in the activation of MITF transcriptional activity. Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation.<ref>PMID:5338216</ref> <ref>PMID:15851690</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 4dpg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4dpg" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Aminoacyl tRNA synthetase 3D structures\|Aminoacyl tRNA synthetase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Lysine--tRNA ligase~~]]		[[Category: Large Structures]]
	[[Category: Bennett~~, S P~~]]		[[Category: Bennett SP]]
	[[Category: Fang, P]]		[[Category: Fang P]]
	[[Category: Guo, M]]		[[Category: Guo M]]
	[[Category: Wang, J]]		[[Category: Wang J]]
	~~[[Category: Aimp2]]~~
	~~[[Category: Ligase-apoptosis complex]]~~
	~~[[Category: Lysr]]~~
	~~[[Category: Lysyl-trna synthetase]]~~
	~~[[Category: Multi trna synthetase complex sub-complex]]~~
	~~[[Category: P38~~]]

OCA at 02:43, 11 December 2016

2016-12-11T02:43:11Z

← Older revision		Revision as of 02:43, 11 December 2016
Line 1:		Line 1:

	==Crystal Structure of Human LysRS: P38/AIMP2 Complex I==		==Crystal Structure of Human LysRS: P38/AIMP2 Complex I==
	<StructureSection load='4dpg' size='340' side='right' caption='[[4dpg]], [[Resolution\|resolution]] 2.84Å' scene=''>		<StructureSection load='4dpg' size='340' side='right' caption='[[4dpg]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dpg]] is a 12 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=4DPG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DPG FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dpg]] is a 12 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=4DPG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DPG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dpj\|4dpj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dpj\|4dpj]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KARS, KIAA0070 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), AIMP2, JTV1, PRO0992 ([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">KARS, KIAA0070 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), AIMP2, JTV1, PRO0992 ([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/Lysine--tRNA_ligase Lysine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.6 6.1.1.6] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysine--tRNA_ligase Lysine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.6 6.1.1.6] </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=4dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dpg RCSB], [http://www.ebi.ac.uk/pdbsum/4dpg 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=4dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpg OCA], [http://pdbe.org/4dpg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dpg RCSB], [http://www.ebi.ac.uk/pdbsum/4dpg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dpg 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 4dpg" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Lysine--tRNA ligase]]		[[Category: Lysine--tRNA ligase]]
	[[Category: Bennett, S P]]		[[Category: Bennett, S P]]

OCA at 15:46, 9 December 2014

2014-12-09T15:46:42Z

← Older revision		Revision as of 15:46, 9 December 2014
Line 1:		Line 1:
	[[~~Image~~:~~4dpg~~.~~jpg~~\|~~left~~\|~~200px~~]]		==Crystal Structure of Human LysRS: P38/AIMP2 Complex I==
			<StructureSection load='4dpg' size='340' side='right' caption='[[4dpg]], [[Resolution\|resolution]] 2.84Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4dpg]] is a 12 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=4DPG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DPG FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dpj\|4dpj]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KARS, KIAA0070 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), AIMP2, JTV1, PRO0992 ([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/Lysine--tRNA_ligase Lysine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.6 6.1.1.6] </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=4dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dpg RCSB], [http://www.ebi.ac.uk/pdbsum/4dpg PDBsum]</span></td></tr>
			</table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/SYK_HUMAN SYK_HUMAN]] Defects in KARS are the cause of Charcot-Marie-Tooth disease recessive intermediate type B (CMTRIB) [MIM:[http://omim.org/entry/613641 613641]]; also called Charcot-Marie-Tooth neuropathy recessive intermediate B. CMTRIB is a form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.<ref>PMID:20920668</ref>
			== Function ==
			[[http://www.uniprot.org/uniprot/SYK_HUMAN SYK_HUMAN]] Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages. Catalyzes the synthesis of diadenosine oligophosphate (Ap4A), a signaling molecule involved in the activation of MITF transcriptional activity. Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation.<ref>PMID:5338216</ref> <ref>PMID:15851690</ref> [[http://www.uniprot.org/uniprot/AIMP2_HUMAN AIMP2_HUMAN]] Required for assembly and stability of the aminoacyl-tRNA synthase complex. Mediates ubiquitination and degradation of FUBP1, a transcriptional activator of MYC, leading to MYC down-regulation which is required for aveolar type II cell differentiation. Blocks MDM2-mediated ubiquitination and degradation of p53/TP53. Functions as a proapoptotic factor.<ref>PMID:16135753</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Lysyl-tRNA synthetase (LysRS), a component of the translation apparatus, is released from the cytoplasmic multi-tRNA synthetase complex (MSC) to activate the transcription factor MITF in stimulated mast cells through undefined mechanisms. Here we show that Ser207 phosphorylation provokes a new conformer of LysRS that inactivates its translational function but activates its transcriptional function. The crystal structure of an MSC subcomplex established that LysRS is held in the MSC by binding to the N terminus of the scaffold protein p38/AIMP2. Phosphorylation-created steric clashes at the LysRS domain interface disrupt its binding grooves for p38/AIMP2, releasing LysRS and provoking its nuclear translocation. This alteration also exposes the C-terminal domain of LysRS to bind to MITF and triggers LysRS-directed production of the second messenger Ap(4)A that activates MITF. Thus our results establish that a single conformational change triggered by phosphorylation leads to multiple effects driving an exclusive switch of LysRS function from translation to transcription.

	~~{{STRUCTURE_4dpg\| PDB=4dpg \| SCENE= }}~~		Structural Switch of Lysyl-tRNA Synthetase between Translation and Transcription.,Ofir-Birin Y, Fang P, Bennett SP, Zhang HM, Wang J, Rachmin I, Shapiro R, Song J, Dagan A, Pozo J, Kim S, Marshall AG, Schimmel P, Yang XL, Nechushtan H, Razin E, Guo M Mol Cell. 2013 Jan 10;49(1):30-42. doi: 10.1016/j.molcel.2012.10.010. Epub 2012, Nov 15. PMID:23159739<ref>PMID:23159739</ref>

	~~===Crystal Structure~~ of ~~Human LysRS: P38~~/~~AIMP2 Complex I===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~{{ABSTRACT_PUBMED_23159739}}~~		== References ==
			<references/>
	==~~About this Structure~~==		__TOC__
	~~[[4dpg]] is a 12 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=4DPG OCA].~~		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Lysine--tRNA ligase]]		[[Category: Lysine--tRNA ligase]]
	[[Category: Bennett, S P.]]		[[Category: Bennett, S P]]
	[[Category: Fang, P.]]		[[Category: Fang, P]]
	[[Category: Guo, M.]]		[[Category: Guo, M]]
	[[Category: Wang, J.]]		[[Category: Wang, J]]
	[[Category: Aimp2]]		[[Category: Aimp2]]
	[[Category: Ligase-apoptosis complex]]		[[Category: Ligase-apoptosis complex]]

OCA at 10:33, 13 February 2013

2013-02-13T10:33:05Z

← Older revision		Revision as of 10:33, 13 February 2013
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	~~'''Unreleased structure'''~~		[[Image:4dpg.jpg\|left\|200px]]

	~~The entry~~ 4dpg ~~is ON HOLD~~ ~~until Feb 12 2014~~		{{STRUCTURE_4dpg\| PDB=4dpg \| SCENE= }}

	~~Authors~~: ~~Fang, P., Wang, J., Bennett, S.P., Guo, M.~~		===Crystal Structure of Human LysRS: P38/AIMP2 Complex I===

	~~Description~~: ~~Crystal Structure of Human LysRS~~: P38~~/AIMP2 Complex I~~		{{ABSTRACT_PUBMED_23159739}}

			==About this Structure==
			[[4dpg]] is a 12 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=4DPG OCA].
			[[Category: Homo sapiens]]
			[[Category: Lysine--tRNA ligase]]
			[[Category: Bennett, S P.]]
			[[Category: Fang, P.]]
			[[Category: Guo, M.]]
			[[Category: Wang, J.]]
			[[Category: Aimp2]]
			[[Category: Ligase-apoptosis complex]]
			[[Category: Lysr]]
			[[Category: Lysyl-trna synthetase]]
			[[Category: Multi trna synthetase complex sub-complex]]
			[[Category: P38]]

OCA at 10:59, 23 January 2013

2013-01-23T10:59:58Z

← Older revision		Revision as of 10:59, 23 January 2013
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4dpg is ON HOLD until ~~Paper Publication~~		The entry 4dpg is ON HOLD until Feb 12 2014

	Authors: Fang, P., Wang, J., Bennett, S.P., Guo, M.		Authors: Fang, P., Wang, J., Bennett, S.P., Guo, M.

	Description: Crystal Structure of Human LysRS: P38/AIMP2 Complex I		Description: Crystal Structure of Human LysRS: P38/AIMP2 Complex I

OCA: Protected "4dpg" [edit=sysop:move=sysop]

2012-02-22T07:32:04Z

Protected "4dpg" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:32, 22 February 2012
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4dpg is ON HOLD until Paper Publication Authors: Fang, P., Wang, J., Bennett, S.P., Guo, M. Description: Crystal Structure of Human LysRS: P38/AIMP...

2012-02-22T07:32:02Z

New page: '''Unreleased structure''' The entry 4dpg is ON HOLD until Paper Publication Authors: Fang, P., Wang, J., Bennett, S.P., Guo, M. Description: Crystal Structure of Human LysRS: P38/AIMP...

New page

'''Unreleased structure'''

The entry 4dpg is ON HOLD until Paper Publication

Authors: Fang, P., Wang, J., Bennett, S.P., Guo, M.

Description: Crystal Structure of Human LysRS: P38/AIMP2 Complex I