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| - | [[Image:3bju.jpg|left|200px]]<br /><applet load="3bju" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="3bju, resolution 2.31Å" /> | |
| - | '''Crystal Structure of tetrameric form of human lysyl-tRNA synthetase'''<br /> | |
| | | | |
| - | ==About this Structure== | + | ==Crystal Structure of tetrameric form of human lysyl-tRNA synthetase== |
| - | 3BJU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=LYS:'>LYS</scene> and <scene name='pdbligand=ATP:'>ATP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Sites: <scene name='pdbsite=AC1:Ca+Binding+Site+For+Residue+B+606'>AC1</scene>, <scene name='pdbsite=AC2:Ca+Binding+Site+For+Residue+B+607'>AC2</scene>, <scene name='pdbsite=AC3:Ca+Binding+Site+For+Residue+B+608'>AC3</scene>, <scene name='pdbsite=AC4:Ca+Binding+Site+For+Residue+C+606'>AC4</scene>, <scene name='pdbsite=AC5:Ca+Binding+Site+For+Residue+C+607'>AC5</scene>, <scene name='pdbsite=AC6:Ca+Binding+Site+For+Residue+C+608'>AC6</scene>, <scene name='pdbsite=AC7:Ca+Binding+Site+For+Residue+D+606'>AC7</scene>, <scene name='pdbsite=AC8:Ca+Binding+Site+For+Residue+D+607'>AC8</scene>, <scene name='pdbsite=AC9:Ca+Binding+Site+For+Residue+D+608'>AC9</scene>, <scene name='pdbsite=BC1:Ca+Binding+Site+For+Residue+A+606'>BC1</scene>, <scene name='pdbsite=BC2:Ca+Binding+Site+For+Residue+A+607'>BC2</scene>, <scene name='pdbsite=BC3:Ca+Binding+Site+For+Residue+A+608'>BC3</scene>, <scene name='pdbsite=BC4:LYS+Binding+Site+For+Residue+B+601'>BC4</scene>, <scene name='pdbsite=BC5:Atp+Binding+Site+For+Residue+B+603'>BC5</scene>, <scene name='pdbsite=BC6:LYS+Binding+Site+For+Residue+C+601'>BC6</scene>, <scene name='pdbsite=BC7:Atp+Binding+Site+For+Residue+C+603'>BC7</scene>, <scene name='pdbsite=BC8:LYS+Binding+Site+For+Residue+D+601'>BC8</scene>, <scene name='pdbsite=BC9:Atp+Binding+Site+For+Residue+D+603'>BC9</scene>, <scene name='pdbsite=CC1:LYS+Binding+Site+For+Residue+A+601'>CC1</scene> and <scene name='pdbsite=CC2:Atp+Binding+Site+For+Residue+A+603'>CC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BJU OCA].
| + | <StructureSection load='3bju' size='340' side='right'caption='[[3bju]], [[Resolution|resolution]] 2.31Å' scene=''> |
| - | [[Category: Homo sapiens]] | + | == Structural highlights == |
| - | [[Category: Lysine--tRNA ligase]] | + | <table><tr><td colspan='2'>[[3bju]] is a 4 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=3BJU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BJU FirstGlance]. <br> |
| - | [[Category: Single protein]] | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31Å</td></tr> |
| - | [[Category: Guo, M.]]
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene></td></tr> |
| - | [[Category: Schimmel, P.]] | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bju FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bju OCA], [https://pdbe.org/3bju PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bju RCSB], [https://www.ebi.ac.uk/pdbsum/3bju PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bju ProSAT]</span></td></tr> |
| - | [[Category: Yang, X.L.]] | + | </table> |
| - | [[Category: ATP]]
| + | == Disease == |
| - | [[Category: CA]]
| + | [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> |
| - | [[Category: LYS]] | + | == Function == |
| - | [[Category: aminoacyl-trna synthetase]]
| + | [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> |
| - | [[Category: atp-binding]]
| + | == Evolutionary Conservation == |
| - | [[Category: cytoplasm]]
| + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | [[Category: ligase]] | + | Check<jmol> |
| - | [[Category: lysyl-trna]] | + | <jmolCheckbox> |
| - | [[Category: nucleotide-binding]] | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bj/3bju_consurf.spt"</scriptWhenChecked> |
| - | [[Category: phosphoprotein]] | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | [[Category: polymorphism]]
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | [[Category: protein biosynthesis]]
| + | </jmolCheckbox> |
| - | [[Category: trna synthetase]]
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bju ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | In mammals, many aminoacyl-tRNA synthetases are bound together in a multisynthetase complex (MSC) as a reservoir of procytokines and regulation molecules for functions beyond aminoacylation. The alpha(2) homodimeric lysyl-tRNA synthetase (LysRS) is tightly bound in the MSC and, under specific conditions, is secreted to trigger a proinflammatory response. Results by others suggest that alpha(2) LysRS is tightly bound into the core of the MSC with homodimeric beta(2) p38, a scaffolding protein that itself is multifunctional. Not understood is how the two dimeric proteins combine to make a presumptive alpha(2)beta(2) heterotetramer and, in particular, the location of the surfaces on LysRS that would accommodate the p38 interactions. Here we present a 2.3-A crystal structure of a tetrameric form of human LysRS. The relatively loose (as seen in solution) tetramer interface is assembled from two eukaryote-specific sequences, one in the catalytic- and another in the anticodon-binding domain. This same interface is predicted to provide unique determinants for interaction with p38. The analyses suggest how the core of the MSC is assembled and, more generally, that interactions and functions of synthetases can be built and regulated through dynamic protein-protein interfaces. These interfaces are created from small adaptations to what is otherwise a highly conserved (through evolution) polypeptide sequence. |
| | | | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 13 08:15:27 2008''
| + | Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation.,Guo M, Ignatov M, Musier-Forsyth K, Schimmel P, Yang XL Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2331-6. Epub 2008 Feb 13. PMID:18272479<ref>PMID:18272479</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 3bju" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | + | [[Category: Large Structures]] |
| | + | [[Category: Guo M]] |
| | + | [[Category: Schimmel P]] |
| | + | [[Category: Yang XL]] |
| Structural highlights
Disease
SYK_HUMAN Defects in KARS are the cause of Charcot-Marie-Tooth disease recessive intermediate type B (CMTRIB) [MIM: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.[1]
Function
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.[2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
In mammals, many aminoacyl-tRNA synthetases are bound together in a multisynthetase complex (MSC) as a reservoir of procytokines and regulation molecules for functions beyond aminoacylation. The alpha(2) homodimeric lysyl-tRNA synthetase (LysRS) is tightly bound in the MSC and, under specific conditions, is secreted to trigger a proinflammatory response. Results by others suggest that alpha(2) LysRS is tightly bound into the core of the MSC with homodimeric beta(2) p38, a scaffolding protein that itself is multifunctional. Not understood is how the two dimeric proteins combine to make a presumptive alpha(2)beta(2) heterotetramer and, in particular, the location of the surfaces on LysRS that would accommodate the p38 interactions. Here we present a 2.3-A crystal structure of a tetrameric form of human LysRS. The relatively loose (as seen in solution) tetramer interface is assembled from two eukaryote-specific sequences, one in the catalytic- and another in the anticodon-binding domain. This same interface is predicted to provide unique determinants for interaction with p38. The analyses suggest how the core of the MSC is assembled and, more generally, that interactions and functions of synthetases can be built and regulated through dynamic protein-protein interfaces. These interfaces are created from small adaptations to what is otherwise a highly conserved (through evolution) polypeptide sequence.
Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation.,Guo M, Ignatov M, Musier-Forsyth K, Schimmel P, Yang XL Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2331-6. Epub 2008 Feb 13. PMID:18272479[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ McLaughlin HM, Sakaguchi R, Liu C, Igarashi T, Pehlivan D, Chu K, Iyer R, Cruz P, Cherukuri PF, Hansen NF, Mullikin JC, Biesecker LG, Wilson TE, Ionasescu V, Nicholson G, Searby C, Talbot K, Vance JM, Zuchner S, Szigeti K, Lupski JR, Hou YM, Green ED, Antonellis A. Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy. Am J Hum Genet. 2010 Oct 8;87(4):560-6. doi: 10.1016/j.ajhg.2010.09.008. PMID:20920668 doi:10.1016/j.ajhg.2010.09.008
- ↑ Zamecnik PC, Stephenson ML, Janeway CM, Randerath K. Enzymatic synthesis of diadenosine tetraphosphate and diadenosine triphosphate with a purified lysyl-sRNA synthetase. Biochem Biophys Res Commun. 1966 Jul 6;24(1):91-7. PMID:5338216
- ↑ Park SG, Kim HJ, Min YH, Choi EC, Shin YK, Park BJ, Lee SW, Kim S. Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response. Proc Natl Acad Sci U S A. 2005 May 3;102(18):6356-61. Epub 2005 Apr 25. PMID:15851690 doi:10.1073/pnas.0500226102
- ↑ Guo M, Ignatov M, Musier-Forsyth K, Schimmel P, Yang XL. Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2331-6. Epub 2008 Feb 13. PMID:18272479
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