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6ild

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Revision as of 07:52, 10 April 2019

Crystal Structure of Human LysRS: P38/AIMP2 Complex II

Structural highlights

6ild is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	KARS, KIAA0070 (HUMAN), AIMP2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [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.^[4]

Publication Abstract from PubMed

Multi-aminoacyl-tRNA synthetase complex (MSC) is the second largest machinery for protein synthesis in human cells and also regulates multiple nontranslational functions through its components. Previous studies have shown that the MSC can respond to external signals by releasing its components to function outside it. The internal assembly is fundamental to MSC regulation. Here, using crystal structural analyses (at 1.88 A resolution) along with molecular modeling, gel filtration chromatography, and co-immunoprecipitation, we report that human lysyl-tRNA synthetase (LysRS) forms a tighter assembly with the scaffold protein aminoacyl-tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) than previously observed. We found that two AIMP2 N-terminal peptides form an antiparallel scaffold and hold two LysRS dimers through four binding motifs and additional interactions. Of note, the four catalytic subunits of LysRS in the tightly assembled complex were all accessible for tRNA recognition. We further noted that two recently reported human disease-associated mutations conflict with this tighter assembly, cause LysRS release from the MSC, and inactivate the enzyme. These findings reveal a previously unknown dimension of MSC subcomplex assembly and suggest that the retractility of this complex may be critical for its physiological functions.

Retractile lysyl-tRNA synthetase-AIMP2 assembly in the human multi-aminoacyl-tRNA synthetase complex.,Hei Z, Wu S, Liu Z, Wang J, Fang P J Biol Chem. 2019 Feb 7. pii: RA118.006356. doi: 10.1074/jbc.RA118.006356. PMID:30733335^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Ko HS, von Coelln R, Sriram SR, Kim SW, Chung KK, Pletnikova O, Troncoso J, Johnson B, Saffary R, Goh EL, Song H, Park BJ, Kim MJ, Kim S, Dawson VL, Dawson TM. Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death. J Neurosci. 2005 Aug 31;25(35):7968-78. PMID:16135753 doi:25/35/7968
↑ Hei Z, Wu S, Liu Z, Wang J, Fang P. Retractile lysyl-tRNA synthetase-AIMP2 assembly in the human multi-aminoacyl-tRNA synthetase complex. J Biol Chem. 2019 Feb 7. pii: RA118.006356. doi: 10.1074/jbc.RA118.006356. PMID:30733335 doi:http://dx.doi.org/10.1074/jbc.RA118.006356

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6ild"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human LysRS: P38/AIMP2 Complex II==
-<StructureSection load='6ild' size='340' side='right' caption='[[6ild]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
+<StructureSection load='6ild' size='340' side='right'caption='[[6ild]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ild]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ILD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ILD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ild]] is a 3 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=6ILD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ILD FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=45A:5-O-[(S)-HYDROXY(METHYL)PHOSPHORYL]ADENOSINE'>45A</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ild FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ild OCA], [http://pdbe.org/6ild PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ild RCSB], [http://www.ebi.ac.uk/pdbsum/6ild PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ild ProSAT]</span></td></tr>
 </table>
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 6ild" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Fang, P]]
 [[Category: Hei, Z]]

6ild

From Proteopedia

Revision as of 07:52, 10 April 2019

Crystal Structure of Human LysRS: P38/AIMP2 Complex II

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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