Biomolecular NMR Assignments

, Volume 4, Issue 1, pp 41–43

Backbone assignments of the 26 kDa neuron-specific ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1)

  • Fredrik I. Andersson
  • Sophie E. Jackson
  • Shang-Te Danny Hsu


UCH-L1 is a member of the family of ubiquitin C-terminal hydrolases whose primary role is to hydrolyze small C-terminal adducts of ubiquitin to generate free ubiquitin monomers. Expression of UCH-L1 is highly specific to neurons and point mutations in this enzyme are associated with a hereditary form of Parkinson’s disease. Herein, we present the NMR backbone assignments of human UCH-L1, thus enabling future solution-state NMR spectroscopic studies on the structure and function of this important protein.


De-ubiquitination Ubiquitin C-terminal hydrolase Knotted proteins Parkinson’s disease 


  1. Andersson FI, Pina DG, Mallam AL, Blaser G, Jackson SE (2009) Untangling the folding mechanism of the 5(2)-knotted protein UCH-L3. FEBS J 276:2625–2635CrossRefGoogle Scholar
  2. Carmine Belin A, Westerlund M, Bergman O, Nissbrandt H, Lind C, Sydow O, Galter D (2007) S18Y in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) associated with decreased risk of Parkinson’s disease in Sweden. Parkinsonism Relat Disord 13:295–298CrossRefGoogle Scholar
  3. Choi J, Levey AI, Weintraub ST, Rees HD, Gearing M, Chin L-S, Li L (2004) Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson’s and Alzheimer’s diseases. J Biol Chem 279:13256–13264CrossRefGoogle Scholar
  4. Das C, Hoang QQ, Kreinbring CA, Luchansky SJ, Meray RK, Ray SS, Lansbury PT, Ringe D, Petsko GA (2006) Structural basis for conformational plasticity of the Parkinson’s disease-associated ubiquitin hydrolase UCH-L1. Proc Natl Acad Sci USA 103:4675–4680CrossRefADSGoogle Scholar
  5. Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfeifer J, Bax A (1995) NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR 6:277–293CrossRefGoogle Scholar
  6. De Simone A, Cavalli A, Hsu S-TD, Vranken W, Vendruscolo M (2009) Accurate random coil chemical shifts from an analysis of loop regions in native states of proteins. J Am Chem Soc 131:16332–16333CrossRefGoogle Scholar
  7. Goddard TD, Kneller DG Sparky 3. University of California, San Fransisco.
  8. Harris R, Eidhoff U, Vinzenz D, Renatus M, Gerhartz B, Hommel U, Driscoll PC (2007) Backbone 1H, 13C, and 15N resonance assignments for the 26-kD human de-ubiquitinating enzyme UCH-L3. Biomol NMR Assign 1:51–53CrossRefGoogle Scholar
  9. Hsu S-TD, Dobson CM (2009) 1H, 15N and 13C assignments of the dimeric ribosome binding domain of trigger factor from Escherichia coli. Biomol NMR Assign 3:17–20CrossRefGoogle Scholar
  10. Johnston SC, Larsen CN, Cook WJ, Wilkinson KD, Hill CP (1997) Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution. EMBO J 16:3787–3796CrossRefGoogle Scholar
  11. Larsen CN, Price JS, Wilkinson KD (1996) Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues. Biochemistry 35:6735–6744CrossRefGoogle Scholar
  12. Liu C, Miller H, Kohr W, Silber J (1989) Purification of a ubiquitin protein peptidase from yeast with efficient in vitro assays. J Biol Chem 264:20331–20338Google Scholar
  13. Sattler M, Schleucher J, Griesinger C (1999) Heteronuclear multidimensional NMR experiments for the structure determination of proteins in solution employing pulsed field gradients. Prog Nucl Magn Reson Spectrosc 34:93–158CrossRefGoogle Scholar
  14. Virnau P, Mirny LA, Kardar M (2006) Intricate knots in proteins: function and evolution. PLoS Comput Biol 2:1074–1079CrossRefGoogle Scholar
  15. Wilkinson K, Lee K, Deshpande S, Duerksen-Hughes P, Boss J, Pohl J (1989) The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Science 246:670–673CrossRefADSGoogle Scholar
  16. Zhang N, Wilkinson K, Bownes M (1993) Cloning and analysis of expression of a ubiquitin carboxyl terminal hydrolase expressed during oogenesis in Drosophila melanogaster. Dev Biol 157:214–223CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Fredrik I. Andersson
    • 1
  • Sophie E. Jackson
    • 1
  • Shang-Te Danny Hsu
    • 1
  1. 1.Department of ChemistryUniversity of CambridgeCambridgeUK

Personalised recommendations