Skip to main content
SpringerLink
Log in
Book cover

Aminoacyl-tRNA Synthetases in Biology and Medicine pp 89–118Cite as

Architecture and Metamorphosis

  • Chapter
  • First Online:

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 344))

Abstract

When compared to other conserved housekeeping protein families, such as ribosomal proteins, during the evolution of higher eukaryotes, aminoacyl-tRNA synthetases (aaRSs) show an apparent high propensity to add new sequences, and especially new domains. The stepwise emergence of those new domains is consistent with their involvement in a broad range of biological functions beyond protein synthesis, and correlates with the increasing biological complexity of higher organisms. These new domains have been extensively characterized based on their evolutionary origins and their sequence, structural, and functional features. While some of the domains are uniquely found in aaRSs and may have originated from nucleic acid binding motifs, others are common domain modules mediating protein–protein interactions that play a critical role in the assembly of the multi-synthetase complex (MSC). Interestingly, the MSC has emerged from a miniature complex in yeast to a large stable complex in humans. The human MSC consists of nine aaRSs (LysRS, ArgRS, GlnRS, AspRS, MetRS, IleRS, LeuRS, GluProRS, and bifunctional aaRs) and three scaffold proteins (AIMP1/p43, AIMP2/p38, and AIMP3/p18), and has a molecular weight of 1.5 million Dalton. The MSC has been proposed to have a functional dualism: facilitating protein synthesis and serving as a reservoir of non-canonical functions associated with its synthetase and non-synthetase components. Importantly, domain additions and functional expansions are not limited to the components of the MSC and are found in almost all aaRS proteins. From a structural perspective, multi-functionalities are represented by multiple conformational states. In fact, alternative conformations of aaRSs have been generated by various mechanisms from proteolysis to alternative splicing and posttranslational modifications, as well as by disease-causing mutations. Therefore, the metamorphosis between different conformational states is connected to the activation and regulation of the novel functions of aaRSs in higher eukaryotes.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   299.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. International Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome. Nature 431(7011):931–945

    Google Scholar 

  2. Mirande M (1991) Aminoacyl-tRNA synthetase family from prokaryotes and eukaryotes: structural domains and their implications. Prog Nucleic Acid Res Mol Biol 40:95–142

    CAS  Google Scholar 

  3. Cheong HK et al (2003) Structure of the N-terminal extension of human aspartyl-tRNA synthetase: implications for its biological function. Int J Biochem Cell Biol 35(11):1548–1557

    CAS  Google Scholar 

  4. Liu S et al (2013) (1)H, (13)C and (15)N resonance assignment of the N-terminal domain of human lysyl aminoacyl tRNA synthetase. Biomol NMR Assign (in press)

    Google Scholar 

  5. Francin M, Mirande M (2003) Functional dissection of the eukaryotic-specific tRNA-interacting factor of lysyl-tRNA synthetase. J Biol Chem 278(3):1472–1479

    CAS  Google Scholar 

  6. Francin M et al (2002) The N-terminal domain of mammalian Lysyl-tRNA synthetase is a functional tRNA-binding domain. J Biol Chem 277(3):1762–1769

    CAS  Google Scholar 

  7. Cen S et al (2004) Ability of wild-type and mutant lysyl-tRNA synthetase to facilitate tRNA(Lys) incorporation into human immunodeficiency virus type 1. J Virol 78(3):1595–1601

    CAS  Google Scholar 

  8. Kim DG et al (2012) Interaction of two translational components, lysyl-tRNA synthetase and p40/37LRP, in plasma membrane promotes laminin-dependent cell migration. FASEB J 26:4142–4159

    CAS  Google Scholar 

  9. Frugier M, Moulinier L, Giege R (2000) A domain in the N-terminal extension of class IIb eukaryotic aminoacyl-tRNA synthetases is important for tRNA binding. EMBO J 19(10):2371–2380

    CAS  Google Scholar 

  10. Escalante C, Yang DC (1993) Expression of human aspartyl-tRNA synthetase in Escherichia coli. Functional analysis of the N-terminal putative amphiphilic helix. J Biol Chem 268(8):6014–6023

    CAS  Google Scholar 

  11. Jacobo-Molina A, Peterson R, Yang DC (1989) cDNA sequence, predicted primary structure, and evolving amphiphilic helix of human aspartyl-tRNA synthetase. J Biol Chem 264(28):16608–16612

    CAS  Google Scholar 

  12. Guo M, Schimmel P, Yang XL (2010) Functional expansion of human tRNA synthetases achieved by structural inventions. FEBS Lett 584(2):434–442

    CAS  Google Scholar 

  13. Renault L et al (2001) Structure of the EMAPII domain of human aminoacyl-tRNA synthetase complex reveals evolutionary dimer mimicry. EMBO J 20(3):570–578

    CAS  Google Scholar 

  14. Morales AJ, Swairjo MA, Schimmel P (1999) Structure-specific tRNA-binding protein from the extreme thermophile Aquifex aeolicus. EMBO J 18(12):3475–3483

    CAS  Google Scholar 

  15. Nomanbhoy T et al (2001) Simultaneous binding of two proteins to opposite sides of a single transfer RNA. Nat Struct Biol 8(4):344–348

    CAS  Google Scholar 

  16. Kaminska M et al (2000) A recurrent general RNA binding domain appended to plant methionyl-tRNA synthetase acts as a cis-acting cofactor for aminoacylation. EMBO J 19(24):6908–6917

    CAS  Google Scholar 

  17. Wakasugi K, Schimmel P (1999) Two distinct cytokines released from a human aminoacyl-tRNA synthetase. Science 284(5411):147–151

    CAS  Google Scholar 

  18. Wakasugi K, Schimmel P (1999) Highly differentiated motifs responsible for two cytokine activities of a split human tRNA synthetase. J Biol Chem 274(33):23155–23159

    CAS  Google Scholar 

  19. Lee PS et al (2012) Uncovering of a short internal peptide activates a tRNA synthetase procytokine. J Biol Chem 287(24):20504–20508

    CAS  Google Scholar 

  20. Bec G, Kerjan P, Waller JP (1994) Reconstitution in vitro of the valyl-tRNA synthetase-elongation factor (EF) 1 beta gamma delta complex. Essential roles of the NH2-terminal extension of valyl-tRNA synthetase and of the EF-1 delta subunit in complex formation. J Biol Chem 269(3):2086–2092

    CAS  Google Scholar 

  21. Negrutskii BS et al (1999) Functional interaction of mammalian valyl-tRNA synthetase with elongation factor EF-1alpha in the complex with EF-1H. J Biol Chem 274(8):4545–4550

    CAS  Google Scholar 

  22. Guo M, Yang XL, Schimmel P (2010) New functions of aminoacyl-tRNA synthetases beyond translation. Nat Rev Mol Cell Biol 11(9):668–674

    CAS  Google Scholar 

  23. Simos G et al (1996) The yeast protein Arc1p binds to tRNA and functions as a cofactor for the methionyl- and glutamyl-tRNA synthetases. EMBO J 15(19):5437–5448

    CAS  Google Scholar 

  24. He R et al (2009) Two non-redundant fragments in the N-terminal peptide of human cytosolic methionyl-tRNA synthetase were indispensable for the multi-synthetase complex incorporation and enzyme activity. Biochim Biophys Acta 1794(2):347–354

    CAS  Google Scholar 

  25. Lee SW et al (2004) Aminoacyl-tRNA synthetase complexes: beyond translation. J Cell Sci 117(Pt 17):3725–3734

    CAS  Google Scholar 

  26. Simader H et al (2006) Structural basis of yeast aminoacyl-tRNA synthetase complex formation revealed by crystal structures of two binary sub-complexes. Nucleic Acids Res 34(14):3968–3979

    CAS  Google Scholar 

  27. Koonin EV et al (1994) Eukaryotic translation elongation factor 1 gamma contains a glutathione transferase domain – study of a diverse, ancient protein superfamily using motif search and structural modeling. Protein Sci 3(11):2045–2054

    CAS  Google Scholar 

  28. Tang SS, Chang GG (1996) Kinetic characterization of the endogenous glutathione transferase activity of octopus lens S-crystallin. J Biochem 119(6):1182–1188

    CAS  Google Scholar 

  29. Kobayashi S, Kidou S, Ejiri S (2001) Detection and characterization of glutathione S-transferase activity in rice EF-1betabeta′gamma and EF-1gamma expressed in Escherichia coli. Biochem Biophys Res Commun 288(3):509–514

    CAS  Google Scholar 

  30. Kim JY et al (2002) p38 is essential for the assembly and stability of macromolecular tRNA synthetase complex: implications for its physiological significance. Proc Natl Acad Sci U S A 99(12):7912–7916

    CAS  Google Scholar 

  31. Rho SB et al (1999) Genetic dissection of protein-protein interactions in multi-tRNA synthetase complex. Proc Natl Acad Sci U S A 96(8):4488–4493

    CAS  Google Scholar 

  32. Quevillon S et al (1999) Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein. J Mol Biol 285(1):183–195

    CAS  Google Scholar 

  33. Kim JE et al (2000) An elongation factor-associating domain is inserted into human cysteinyl-tRNA synthetase by alternative splicing. Nucleic Acids Res 28(15):2866–2872

    CAS  Google Scholar 

  34. Takeda J et al (2008) Low conservation and species-specific evolution of alternative splicing in humans and mice: comparative genomics analysis using well-annotated full-length cDNAs. Nucleic Acids Res 36(20):6386–6395

    CAS  Google Scholar 

  35. Shiba K (2002) Intron positions delineate the evolutionary path of a pervasively appended peptide in five human aminoacyl-tRNA synthetases. J Mol Evol 55(6):727–733

    CAS  Google Scholar 

  36. Brenner S, Corrochano LM (1996) Translocation events in the evolution of aminoacyl-tRNA synthetases. Proc Natl Acad Sci U S A 93(16):8485–8489

    CAS  Google Scholar 

  37. Ray PS et al (2011) Evolution of function of a fused metazoan tRNA synthetase. Mol Biol Evol 28(1):437–447

    CAS  Google Scholar 

  38. Rho SB et al (1998) A multifunctional repeated motif is present in human bifunctional tRNA synthetase. J Biol Chem 273(18):11267–11273

    CAS  Google Scholar 

  39. Maris C, Dominguez C, Allain FH (2005) The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression. FEBS J 272(9):2118–2131

    CAS  Google Scholar 

  40. Ting SM, Bogner P, Dignam JD (1992) Isolation of prolyl-tRNA synthetase as a free form and as a form associated with glutamyl-tRNA synthetase. J Biol Chem 267(25):17701–17709

    CAS  Google Scholar 

  41. Ewalt KL et al (2005) Variant of human enzyme sequesters reactive intermediate. Biochemistry 44(11):4216–4221

    CAS  Google Scholar 

  42. Cahuzac B et al (2000) A recurrent RNA-binding domain is appended to eukaryotic aminoacyl-tRNA synthetases. EMBO J 19(3):445–452

    CAS  Google Scholar 

  43. Sampath P et al (2004) Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation. Cell 119(2):195–208

    CAS  Google Scholar 

  44. Arif A et al (2009) Two-site phosphorylation of EPRS coordinates multimodal regulation of noncanonical translational control activity. Mol Cell 35(2):164–180

    CAS  Google Scholar 

  45. Jia J et al (2008) WHEP domains direct noncanonical function of glutamyl-Prolyl tRNA synthetase in translational control of gene expression. Mol Cell 29(6):679–690

    CAS  Google Scholar 

  46. Kapasi P et al (2007) L13a blocks 48S assembly: role of a general initiation factor in mRNA-specific translational control. Mol Cell 25(1):113–126

    CAS  Google Scholar 

  47. Ilyin VA et al (2000) 2.9 A crystal structure of ligand-free tryptophanyl-tRNA synthetase: domain movements fragment the adenine nucleotide binding site. Protein Sci 9(2):218–231

    CAS  Google Scholar 

  48. Tzima E et al (2003) Biologically active fragment of a human tRNA synthetase inhibits fluid shear stress-activated responses of endothelial cells. Proc Natl Acad Sci U S A 100(25):14903–14907

    CAS  Google Scholar 

  49. Wakasugi K et al (2002) A human aminoacyl-tRNA synthetase as a regulator of angiogenesis. Proc Natl Acad Sci U S A 99(1):173–177

    CAS  Google Scholar 

  50. Otani A et al (2002) A fragment of human TrpRS as a potent antagonist of ocular angiogenesis. Proc Natl Acad Sci U S A 99(1):178–183

    CAS  Google Scholar 

  51. Sajish M et al (2012) Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-gamma and p53 signaling. Nat Chem Biol 8:547–554

    CAS  Google Scholar 

  52. Sutton RB et al (1998) Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature 395(6700):347–353

    CAS  Google Scholar 

  53. Chan DC et al (1997) Core structure of gp41 from the HIV envelope glycoprotein. Cell 89(2):263–273

    CAS  Google Scholar 

  54. Ahn HC, Kim S, Lee BJ (2003) Solution structure and p43 binding of the p38 leucine zipper motif: coiled-coil interactions mediate the association between p38 and p43. FEBS Lett 542(1–3):119–124

    CAS  Google Scholar 

  55. Deutscher MP, Ni RC (1982) Purification of a low molecular weight form of rat liver arginyl-tRNA synthetase. J Biol Chem 257(11):6003–6006

    CAS  Google Scholar 

  56. Vellekamp G, Sihag RK, Deutscher MP (1985) Comparison of the complexed and free forms of rat liver arginyl-tRNA synthetase and origin of the free form. J Biol Chem 260(17):9843–9847

    CAS  Google Scholar 

  57. Zheng YG et al (2006) Two forms of human cytoplasmic arginyl-tRNA synthetase produced from two translation initiations by a single mRNA. Biochemistry 45(4):1338–1344

    CAS  Google Scholar 

  58. Shiba K et al (1994) Human cytoplasmic isoleucyl-tRNA synthetase: selective divergence of the anticodon-binding domain and acquisition of a new structural unit. Proc Natl Acad Sci U S A 91(16):7435–7439

    CAS  Google Scholar 

  59. Rho SB et al (1996) Interaction between human tRNA synthetases involves repeated sequence elements. Proc Natl Acad Sci U S A 93(19):10128–10133

    CAS  Google Scholar 

  60. Segev N, Hay N (2012) Hijacking leucyl-tRNA synthetase for amino acid-dependent regulation of TORC1. Mol Cell 46(1):4–6

    CAS  Google Scholar 

  61. Han JM et al (2012) Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 149:410–424

    CAS  Google Scholar 

  62. Bonfils G et al (2012) Leucyl-tRNA synthetase controls TORC1 via the EGO complex. Mol Cell 46(1):105–110

    CAS  Google Scholar 

  63. Finarov I et al (2010) Structure of human cytosolic phenylalanyl-tRNA synthetase: evidence for kingdom-specific design of the active sites and tRNA binding patterns. Structure 18(3):343–353

    CAS  Google Scholar 

  64. Dou X, Limmer S, Kreutzer R (2001) DNA-binding of phenylalanyl-tRNA synthetase is accompanied by loop formation of the double-stranded DNA. J Mol Biol 305(3):451–458

    CAS  Google Scholar 

  65. Crepin T et al (2011) A hybrid structural model of the complete Brugia malayi cytoplasmic asparaginyl-tRNA synthetase. J Mol Biol 405(4):1056–1069

    CAS  Google Scholar 

  66. Grant TD et al (2012) Structural conservation of an ancient tRNA sensor in eukaryotic glutaminyl-tRNA synthetase. Nucleic Acids Res 40(8):3723–3731

    CAS  Google Scholar 

  67. Xu XL et al (2012) Unique domain appended to vertebrate tRNA synthetase is essential for vascular development. Nat Commun 3

    Google Scholar 

  68. Herzog W et al (2009) Genetic evidence for a noncanonical function of seryl-tRNA synthetase in vascular development. Circ Res 104(11):1260–1266

    CAS  Google Scholar 

  69. Fukui H, Hanaoka R, Kawahara A (2009) Noncanonical activity of seryl-tRNA synthetase is involved in vascular development. Circ Res 104(11):1253–1259

    CAS  Google Scholar 

  70. Raina M et al (2012) Association of a multi-synthetase complex with translating ribosomes in the archaeon Thermococcus kodakarensis. FEBS Lett 586(16):2232–2238

    CAS  Google Scholar 

  71. Hausmann CD, Ibba M (2008) Structural and functional mapping of the archaeal multi-aminoacyl-tRNA synthetase complex. FEBS Lett 582(15):2178–2182

    CAS  Google Scholar 

  72. Frechin M et al (2010) Arc1p: anchoring, routing, coordinating. FEBS Lett 584(2):427–433

    CAS  Google Scholar 

  73. Karanasios E, Simos G (2010) Building arks for tRNA: structure and function of the Arc1p family of non-catalytic tRNA-binding proteins. FEBS Lett 584(18):3842–3849

    CAS  Google Scholar 

  74. Kim KJ et al (2008) Determination of three-dimensional structure and residues of the novel tumor suppressor AIMP3/p18 required for the interaction with ATM. J Biol Chem 283(20):14032–14040

    CAS  Google Scholar 

  75. Graindorge JS et al (2005) Role of Arc1p in the modulation of yeast glutamyl-tRNA synthetase activity. Biochemistry 44(4):1344–1352

    CAS  Google Scholar 

  76. Wiltrout E et al (2012) Misacylation of tRNA with methionine in Saccharomyces cerevisiae. Nucleic Acids Res 40:10494–10506

    CAS  Google Scholar 

  77. Karanasios E, Boleti H, Simos G (2008) Incorporation of the Arc1p tRNA-binding domain to the catalytic core of MetRS can functionally replace the yeast Arc1p-MetRS complex. J Mol Biol 381(3):763–771

    CAS  Google Scholar 

  78. Galani K et al (2001) The intracellular location of two aminoacyl-tRNA synthetases depends on complex formation with Arc1p. EMBO J 20(23):6889–6898

    CAS  Google Scholar 

  79. Rieger RA et al (2006) Proteomic approach to identification of proteins reactive for abasic sites in DNA. Mol Cell Proteomics 5(5):858–867

    CAS  Google Scholar 

  80. Frechin M, Duchene AM, Becker HD (2009) Translating organellar glutamine codons: a case by case scenario? RNA Biol 6(1):31–34

    CAS  Google Scholar 

  81. Nagao A et al (2009) Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. Proc Natl Acad Sci U S A 106(38):16209–16214

    CAS  Google Scholar 

  82. Rinehart J et al (2005) Saccharomyces cerevisiae imports the cytosolic pathway for Gln-tRNA synthesis into the mitochondrion. Genes Dev 19(5):583–592

    CAS  Google Scholar 

  83. Cook AG et al (2009) Structures of the tRNA export factor in the nuclear and cytosolic states. Nature 461(7260):60–65

    CAS  Google Scholar 

  84. Havrylenko S et al (2011) Caenorhabditis elegans evolves a new architecture for the multi-aminoacyl-tRNA synthetase complex. J Biol Chem 286(32):28476–28487

    CAS  Google Scholar 

  85. Havrylenko S et al (2010) Methionyl-tRNA synthetase from Caenorhabditis elegans: a specific multidomain organization for convergent functional evolution. Protein Sci 19(12):2475–2484

    CAS  Google Scholar 

  86. Kerjan P et al (1994) The multienzyme complex containing nine aminoacyl-tRNA synthetases is ubiquitous from Drosophila to mammals. Biochim Biophys Acta 1199(3):293–297

    CAS  Google Scholar 

  87. Kyriacou SV, Deutscher MP (2008) An important role for the multienzyme aminoacyl-tRNA synthetase complex in mammalian translation and cell growth. Mol Cell 29(4):419–427

    CAS  Google Scholar 

  88. Ray PS, Arif A, Fox PL (2007) Macromolecular complexes as depots for releasable regulatory proteins. Trends Biochem Sci 32(4):158–164

    CAS  Google Scholar 

  89. Mirande M (2005) Aminoacyl-tRNA synthetases complexes. In: Ibba M, Francklyn C, Cusack S (eds) The aminoacyl-tRNA synthetases. Eurekah, Georgetown, pp 298–308

    Google Scholar 

  90. Wolfe CL et al (2005) A three-dimensional working model of the multienzyme complex of aminoacyl-tRNA synthetases based on electron microscopic placements of tRNA and proteins. J Biol Chem 280(46):38870–38878

    CAS  Google Scholar 

  91. Lazard M, Mirande M, Waller JP (1987) Expression of the aminoacyl-tRNA synthetase complex in cultured Chinese hamster ovary cells. Specific depression of the methionyl-tRNA synthetase component upon methionine restriction. J Biol Chem 262(9):3982–3987

    CAS  Google Scholar 

  92. Park SG, Ewalt KL, Kim S (2005) Functional expansion of aminoacyl-tRNA synthetases and their interacting factors: new perspectives on housekeepers. Trends Biochem Sci 30(10):569–574

    CAS  Google Scholar 

  93. Yannay-Cohen N et al (2009) LysRS serves as a key signaling molecule in the immune response by regulating gene expression. Mol Cell 34(5):603–611

    CAS  Google Scholar 

  94. Ko YG et al (2001) Glutamine-dependent antiapoptotic interaction of human glutaminyl-tRNA synthetase with apoptosis signal-regulating kinase 1. J Biol Chem 276(8):6030–6036

    CAS  Google Scholar 

  95. Park SG, Choi EC, Kim S (2010) Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs): a triad for cellular homeostasis. IUBMB Life 62(4):296–302

    CAS  Google Scholar 

  96. Liu J et al (2011) JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress. EMBO J 30(5):846–858

    CAS  Google Scholar 

  97. Choi JW et al (2009) AIMP2 promotes TNFalpha-dependent apoptosis via ubiquitin-mediated degradation of TRAF2. J Cell Sci 122(Pt 15):2710–2715

    CAS  Google Scholar 

  98. Han JM et al (2008) AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53. Proc Natl Acad Sci U S A 105(32):11206–11211

    CAS  Google Scholar 

  99. Oh YS et al (2010) Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice. Aging Cell 9(5):810–822

    CAS  Google Scholar 

  100. Kwon NH et al (2011) Dual role of methionyl-tRNA synthetase in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein-3. Proc Natl Acad Sci U S A 108(49):19635–19640

    CAS  Google Scholar 

  101. Kaminska M et al (2009) Dissection of the structural organization of the aminoacyl-tRNA synthetase complex. J Biol Chem 284(10):6053–6060

    CAS  Google Scholar 

  102. Han JM, Kim JY, Kim S (2003) Molecular network and functional implications of macromolecular tRNA synthetase complex. Biochem Biophys Res Commun 303(4):985–993

    CAS  Google Scholar 

  103. Norcum MT, Warrington JA (1998) Structural analysis of the multienzyme aminoacyl-tRNA synthetase complex: a three-domain model based on reversible chemical crosslinking. Protein Sci 7(1):79–87

    CAS  Google Scholar 

  104. Robinson JC, Kerjan P, Mirande M (2000) Macromolecular assemblage of aminoacyl-tRNA synthetases: quantitative analysis of protein-protein interactions and mechanism of complex assembly. J Mol Biol 304(5):983–994

    CAS  Google Scholar 

  105. Han JM et al (2006) Hierarchical network between the components of the multi-tRNA synthetase complex: implications for complex formation. J Biol Chem 281(50):38663–38667

    CAS  Google Scholar 

  106. Ofir-Birin Y et al (2013) Structural switch of lysyl-tRNA synthetases between translation and transcription. Mol Cell 49(1):30–42

    Google Scholar 

  107. Fang P et al (2011) Structural context for mobilization of a human tRNA synthetase from its cytoplasmic complex. Proc Natl Acad Sci U S A 108(20):8239–8244

    CAS  Google Scholar 

  108. Yang XL et al (2002) Crystal structure of a human aminoacyl-tRNA synthetase cytokine. Proc Natl Acad Sci U S A 99(24):15369–15374

    CAS  Google Scholar 

  109. Yang XL et al (2007) Gain-of-function mutational activation of human tRNA synthetase procytokine. Chem Biol 14(12):1323–1333

    CAS  Google Scholar 

  110. Kapoor M et al (2009) Mutational separation of aminoacylation and cytokine activities of human tyrosyl-tRNA synthetase. Chem Biol 16(5):531–539

    CAS  Google Scholar 

  111. Yang XL et al (2007) Functional and crystal structure analysis of active site adaptations of a potent anti-angiogenic human tRNA synthetase. Structure 15(7):793–805

    CAS  Google Scholar 

  112. Tolstrup AB et al (1995) Transcriptional regulation of the interferon-gamma-inducible tryptophanyl-tRNA synthetase includes alternative splicing. J Biol Chem 270(1):397–403

    CAS  Google Scholar 

  113. Shaw AC et al (1999) Mapping and identification of interferon gamma-regulated HeLa cell proteins separated by immobilized pH gradient two-dimensional gel electrophoresis. Electrophoresis 20(4–5):984–993

    CAS  Google Scholar 

  114. Liu J et al (2004) A new gamma-interferon-inducible promoter and splice variants of an anti-angiogenic human tRNA synthetase. Nucleic Acids Res 32(2):719–727

    CAS  Google Scholar 

  115. Zhou Q et al (2010) Orthogonal use of a human tRNA synthetase active site to achieve multifunctionality. Nat Struct Mol Biol 17(1):57–61

    CAS  Google Scholar 

  116. Xu Z et al (2012) Internally deleted human tRNA synthetase suggests evolutionary pressure for repurposing. Structure 20(9):1470–1477

    CAS  Google Scholar 

  117. Choudhary C et al (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325(5942):834–840

    CAS  Google Scholar 

  118. Xirodimas DP et al (2008) Ribosomal proteins are targets for the NEDD8 pathway. EMBO Rep 9(3):280–286

    CAS  Google Scholar 

  119. Jones J et al (2008) A targeted proteomic analysis of the ubiquitin-like modifier nedd8 and associated proteins. J Proteome Res 7(3):1274–1287

    CAS  Google Scholar 

  120. Skre H (1974) Genetic and clinical aspects of Charcot-Marie-Tooth's disease. Clin Genet 6(2):98–118

    CAS  Google Scholar 

  121. Patzko A, Shy ME (2011) Update on Charcot-Marie-Tooth disease. Curr Neurol Neurosci Rep 11(1):78–88

    CAS  Google Scholar 

  122. Nangle LA et al (2007) Charcot-Marie-Tooth disease-associated mutant tRNA synthetases linked to altered dimer interface and neurite distribution defect. Proc Natl Acad Sci U S A 104(27):11239–11244

    CAS  Google Scholar 

  123. Motley WW et al (2011) Charcot-Marie-Tooth-linked mutant GARS is toxic to peripheral neurons independent of wild-type GARS levels. PLoS Genet 7(12):e1002399

    CAS  Google Scholar 

  124. Xie W et al (2007) Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase. Proc Natl Acad Sci U S A 104(24):9976–9981

    CAS  Google Scholar 

  125. He W et al (2011) Dispersed disease-causing neomorphic mutations on a single protein promote the same localized conformational opening. Proc Natl Acad Sci U S A 108(30):12307–12312

    CAS  Google Scholar 

  126. Froelich CA, First EA (2011) Dominant Intermediate Charcot-Marie-Tooth disorder is not due to a catalytic defect in tyrosyl-tRNA synthetase. Biochemistry 50(33):7132–7145

    CAS  Google Scholar 

  127. Storkebaum E et al (2009) Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot-Marie-Tooth neuropathy. Proc Natl Acad Sci U S A 106(28):11782–11787

    CAS  Google Scholar 

  128. Jordanova A et al (2006) Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy. Nat Genet 38(2):197–202

    CAS  Google Scholar 

  129. Antonellis A et al (2003) Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V. Am J Hum Genet 72(5):1293–1299

    CAS  Google Scholar 

  130. Guo M et al (2008) Crystal structure of tetrameric form of human lysyl-tRNA synthetase: implications for multisynthetase complex formation. Proc Natl Acad Sci U S A 105(7):2331–2336

    CAS  Google Scholar 

  131. McLaughlin HM et al (2010) Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy. Am J Hum Genet 87(4):560–566

    CAS  Google Scholar 

  132. Vo MN, Yang XL, Schimmel P (2011) Dissociating quaternary structure regulates cell-signaling functions of a secreted human tRNA synthetase. J Biol Chem 286(13):11563–11568

    CAS  Google Scholar 

  133. Kleiman L, Jones CP, Musier-Forsyth K (2010) Formation of the tRNALys packaging complex in HIV-1. FEBS Lett 584(2):359–365

    CAS  Google Scholar 

  134. Kovaleski BJ et al (2006) In vitro characterization of the interaction between HIV-1 Gag and human lysyl-tRNA synthetase. J Biol Chem 281(28):19449–19456

    CAS  Google Scholar 

  135. Guo M et al (2010) Packaging HIV virion components through dynamic equilibria of a human tRNA synthetase. J Phys Chem B 114(49):16273–16279

    CAS  Google Scholar 

  136. Harris JK et al (2003) The genetic core of the universal ancestor. Genome Res 13(3):407–412

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by US National Institutes of Health (NIH) grants GM 100136 (M.G.) and GM 088278 (X.L.Y).

Author information

Authors and Affiliations

  1. Department of Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL, 33410, USA

    Min Guo

  2. Department of Cancer Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA

    Xiang-Lei Yang

Authors
  1. Min Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiang-Lei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Min Guo or Xiang-Lei Yang .

Editor information

Editors and Affiliations

  1. Department of Molecular Medicine and Biopharmaceutical Sciences, Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Korea, Republic of (South Korea)

    Sunghoon Kim

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Guo, M., Yang, XL. (2013). Architecture and Metamorphosis. In: Kim, S. (eds) Aminoacyl-tRNA Synthetases in Biology and Medicine. Topics in Current Chemistry, vol 344. Springer, Dordrecht. https://doi.org/10.1007/128_2013_424

Download citation

Publish with us

Policies and ethics

Search

Navigation