Uncovering of a Short Internal Peptide Activates a TRNA Synthetase Procytokine

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 May 3

PMID 22549774

Citations 7

Authors

Peter S Lee

Hui-Min Zhang

Alan G Marshall

Xiang-Lei Yang

Paul Schimmel

Affiliations

Soon will be listed here.

Abstract

In higher organisms, aminoacyl-tRNA synthetases developed receptor-mediated ex-translational functions that are activated by various natural mechanisms. Hydrogen-deuterium exchange combined with mass spectrometry and small-angle x-ray scattering showed that activation of the cytokine function of the 528-amino acid human tyrosyl-tRNA synthetase was associated with pinpointed uncovering of a miniature internal ELR tripeptide that triggers receptor signaling. The results reveal the structural simplicity of how the ex-translational function is implemented.

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References

Liu J, Yang X, Ewalt K, Schimmel P . Mutational switching of a yeast tRNA synthetase into a mammalian-like synthetase cytokine. Biochemistry. 2002; 41(48):14232-7. DOI: 10.1021/bi0205395. View

Zhang Z, Smith D . Determination of amide hydrogen exchange by mass spectrometry: a new tool for protein structure elucidation. Protein Sci. 1993; 2(4):522-31. PMC: 2142359. DOI: 10.1002/pro.5560020404. View

Wakasugi K, Schimmel P . Two distinct cytokines released from a human aminoacyl-tRNA synthetase. Science. 1999; 284(5411):147-51. DOI: 10.1126/science.284.5411.147. View

Xu X, Shi Y, Zhang H, Swindell E, Marshall A, Guo M . Unique domain appended to vertebrate tRNA synthetase is essential for vascular development. Nat Commun. 2012; 3:681. PMC: 3293412. DOI: 10.1038/ncomms1686. View

Putnam C, Hammel M, Hura G, Tainer J . X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution. Q Rev Biophys. 2007; 40(3):191-285. DOI: 10.1017/S0033583507004635. View

Vo M, Yang X, Schimmel P . Dissociating quaternary structure regulates cell-signaling functions of a secreted human tRNA synthetase. J Biol Chem. 2011; 286(13):11563-8. PMC: 3064210. DOI: 10.1074/jbc.C110.213876. View

Zhang H, Bou-Assaf G, Emmett M, Marshall A . Fast reversed-phase liquid chromatography to reduce back exchange and increase throughput in H/D exchange monitored by FT-ICR mass spectrometry. J Am Soc Mass Spectrom. 2008; 20(3):520-4. PMC: 2673454. DOI: 10.1016/j.jasms.2008.11.010. View

Wakasugi K, Slike B, Hood J, Ewalt K, Cheresh D, Schimmel P . Induction of angiogenesis by a fragment of human tyrosyl-tRNA synthetase. J Biol Chem. 2002; 277(23):20124-6. DOI: 10.1074/jbc.C200126200. View

Svergun D, Petoukhov M, Koch M . Determination of domain structure of proteins from X-ray solution scattering. Biophys J. 2001; 80(6):2946-53. PMC: 1301478. DOI: 10.1016/S0006-3495(01)76260-1. View

10.

Schaub T, Hendrickson C, Horning S, Quinn J, Senko M, Marshall A . High-performance mass spectrometry: Fourier transform ion cyclotron resonance at 14.5 Tesla. Anal Chem. 2008; 80(11):3985-90. DOI: 10.1021/ac800386h. View

11.

Zhou Q, Kapoor M, Guo M, Belani R, Xu X, Kiosses W . Orthogonal use of a human tRNA synthetase active site to achieve multifunctionality. Nat Struct Mol Biol. 2009; 17(1):57-61. PMC: 3042952. DOI: 10.1038/nsmb.1706. View

12.

Yang X, Kapoor M, Otero F, Slike B, Tsuruta H, Frausto R . Gain-of-function mutational activation of human tRNA synthetase procytokine. Chem Biol. 2007; 14(12):1323-33. PMC: 2693404. DOI: 10.1016/j.chembiol.2007.10.016. View

13.

Martinis S, Plateau P, Cavarelli J, Florentz C . Aminoacyl-tRNA synthetases: a family of expanding functions. Mittelwihr, France, October 10-15, 1999. EMBO J. 1999; 18(17):4591-6. PMC: 1171533. DOI: 10.1093/emboj/18.17.4591. View

14.

Yesylevskyy S, Savytskyi O, Odynets K, Kornelyuk A . Interdomain compactization in human tyrosyl-tRNA synthetase studied by the hierarchical rotations technique. Biophys Chem. 2011; 154(2-3):90-8. DOI: 10.1016/j.bpc.2011.01.005. View

15.

Zhang H, Kazazic S, Schaub T, Tipton J, Emmett M, Marshall A . Enhanced digestion efficiency, peptide ionization efficiency, and sequence resolution for protein hydrogen/deuterium exchange monitored by Fourier transform ion cyclotron resonance mass spectrometry. Anal Chem. 2009; 80(23):9034-41. PMC: 2784605. DOI: 10.1021/ac801417d. View

16.

Han J, Jeong S, Park M, Kim G, Kwon N, Kim H . Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell. 2012; 149(2):410-24. DOI: 10.1016/j.cell.2012.02.044. View

17.

Zhang H, McLoughlin S, Frausto S, Tang H, Emmett M, Marshall A . Simultaneous reduction and digestion of proteins with disulfide bonds for hydrogen/deuterium exchange monitored by mass spectrometry. Anal Chem. 2010; 82(4):1450-4. PMC: 2825376. DOI: 10.1021/ac902550n. View

18.

Kim S, You S, Hwang D . Aminoacyl-tRNA synthetases and tumorigenesis: more than housekeeping. Nat Rev Cancer. 2011; 11(10):708-18. DOI: 10.1038/nrc3124. View

19.

Zhang Z, Li W, Logan T, Li M, G Marshall A . Human recombinant [C22A] FK506-binding protein amide hydrogen exchange rates from mass spectrometry match and extend those from NMR. Protein Sci. 1997; 6(10):2203-17. PMC: 2143553. DOI: 10.1002/pro.5560061015. View

20.

Kazazic S, Zhang H, Schaub T, Emmett M, Hendrickson C, Blakney G . Automated data reduction for hydrogen/deuterium exchange experiments, enabled by high-resolution Fourier transform ion cyclotron resonance mass spectrometry. J Am Soc Mass Spectrom. 2010; 21(4):550-8. PMC: 2901854. DOI: 10.1016/j.jasms.2009.12.016. View