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[[Image:3bju.jpg|left|200px]]


{{Structure
==Crystal Structure of tetrameric form of human lysyl-tRNA synthetase==
|PDB= 3bju |SIZE=350|CAPTION= <scene name='initialview01'>3bju</scene>, resolution 2.31&Aring;
<StructureSection load='3bju' size='340' side='right'caption='[[3bju]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
|SITE= <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>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene> and <scene name='pdbligand=ATP:ADENOSINE-5&#39;-TRIPHOSPHATE'>ATP</scene>
<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>
|ACTIVITY= [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]
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31&#8491;</td></tr>
|GENE= KARS, KIAA0070 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<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>
}}
<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>
</table>
== 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>
== 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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bj/3bju_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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.


'''Crystal Structure of tetrameric form of human lysyl-tRNA synthetase'''
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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3bju" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
 
== References ==
==About this Structure==
<references/>
3BJU is a [[Single protein]] structure of 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=3BJU OCA].
__TOC__
 
</StructureSection>
==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/18272479 18272479]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Lysine--tRNA ligase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Guo M]]
[[Category: Guo, M.]]
[[Category: Schimmel P]]
[[Category: Schimmel, P.]]
[[Category: Yang XL]]
[[Category: Yang, X L.]]
[[Category: ATP]]
[[Category: CA]]
[[Category: LYS]]
[[Category: aminoacyl-trna synthetase]]
[[Category: atp-binding]]
[[Category: cytoplasm]]
[[Category: ligase]]
[[Category: lysyl-trna]]
[[Category: nucleotide-binding]]
[[Category: phosphoprotein]]
[[Category: polymorphism]]
[[Category: protein biosynthesis]]
[[Category: trna synthetase]]
 
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