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  • E-mailAdrian.Drazic@uib.no
  • Visitor Address
    Jonas Lies vei 91
    5009 Bergen
    Room 
    6B106A
  • Postal Address
    Postboks 7804
    5020 Bergen

Identification and characterization of new N-terminal acetyltransferases

Functional role of N-terminal acetylation on cytoskeletal proteins (actin)

Actin is subject to a animal-specific N-terminal (Nt-) maturation process including Nt-arginylation and Nt-acetylation. This unique N-terminal processing towards mature and functional actin forms involves the cotranslational Nt-acetylation of the methionine residue by NatB, followed by posttranslational removal of the acetylated methionine, and then acetylation of the second acidic residues by the recently identified N-terminal acetyltransferase NAA80. However, the beta-actin  isoform can undergo further processing, which is arginylation. The exciting question is why only one actin isoform has two mutually exclusive modifications and how this is decided and regulated by the cell.

Redox regulation of the actin cytoskeleton by Reactive Oxygen Species

Reactive oxygen species (ROS) play a crucial role for the innate immune system of host organisms by killing invading pathogens. ROS are also associated with aging and a series of diseases like cancer, chronic inflammation, pulmonary and neurodegenerative diseases. Upon oxidative stress, actin becomes modified (mainly oxidized) on several positions. This usually results in inhibition of the protein function, nevertheless it is also a powerful tool to regulate actin function as it was shown for the recently discovered MICAL enzymes.

  1. Gebendorfer K.M.*, Drazic A.*, Le Y., Gundlach J., Bepperling A., Kastenmüller A., Ganzinger K.A., Braun N., Franzmann T.M., Winter J. (2012). Identification of a hypochlorite-specific transcription factor from Escherichia coli. J Biol Chem 287, 6892-6903
  2. Drazic A., Miura H., Peschek J., Le Y., Bach N.C., Kriehuber T., Winter J. (2013). Methionine oxidation activates a transcription factor in response to oxidative stress. Proc Natl Acad Sci USA 110, 9493-9498
  3. Drazic A., Tsoutsoulopoulos A., Peschek J., Gundlach J., Krause M., Gebendorfer K.M., Winter, J. (2013). Role of cysteines in the stability and DNA-binding activity of the hypochlorite-specific transcription factor HypT. PLoS One 8, e75683
  4. Drazic A., Gebendorfer K.M., Mak S., Steiner A., Krause M., Bepperling A., Winter J. (2014). Tetramers are the active species of the HOCl-specific transcription factor HypT. J Biol Chem 289, 977-986
  5. Drazic A., Winter J. (2014). The physiological role of reversible methionine oxidation. Biochim Biophys Acta 1844(8):1367-82
  6. Eckl J.M., Drazic A., Rutz D.A., Richter K. (2014) The Nematode Sgt1-homolog D1054.3 binds open and closed Conformations of Hsp90 via distinct Binding Sites. Biochemistry 53, 2505-2014
  7. Haslbeck V., Drazic A., Eckl J.M., Alt F., Helmuth M., Popowicz G, Schmidt W, Braun F, Weiwad M, Fischer G, Gemmecker G, Sattler M, Striggow F, Groll M, Richter K. (2015) Selective activators of protein phosphatase 5 target the auto-inhibitory mechanism. Biosci Rep 35(3), pii: e00210
  8. Drazic A.*, Kutzner E.*, Winter J., Eisenreich W. (2015) Metabolic Response of Escherichia coli upon Treatment with Hypochlorite at Sub-Lethal Concentrations. PLoS One 10(5): e0125823.
  9. Aksnes H., Drazic A., Arnesen T. (2015) (Hyper)tension release by N-terminal acetylation. Trends Biochem Sci 40(8):422-4
  10. Papsdorf K., Kaiser C.J., Drazic A., Grötzinger S.W., Haeßner C., Eisenreich W., Richter K. (2015) Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects. BMC Genomics 16:662
  11. Haslbeck V., Eckl J.M., Drazic A., Rutz D.A., Lorenz O.R., Zimmermann K., Kriehuber T., Lindemann C., Madl T., Richter K. (2015) The activity of protein phosphatase 5 towards native clients is modulated by the middle- and C-terminal domains of Hsp90. Sci Rep 23;5:17058
  12. Drazic A.*, Myklebust L.M.*, Ree R., Arnesen T. (2016) The world of protein acetylation. Biochim Biophys Acta 11;1864(10):1372-1401
  13. Aksnes H.*, Drazic A.*, Marie M.*, Arnesen T. (2016) First Things First: Vital Protein Marks by N-Terminal Acetyltransferases. Trends Biochem Sci pii: S0968-0004(16)30077-9
  14. Aksnes H., Goris M., Strømland Ø., Drazic A., Waheed Q., Reuter N., Arnesen T. (2017) Molecular determinants of the N-terminal acetyltransferase Naa60 anchoring to the Golgi membrane. J Biol Chem 292: 6821-6837
  15. Drazic A., Arnesen T. (2017) [14C]-acetyl-coenzyme A-based in vitro N-terminal acetylation assay. Methods Mol Biol 1574:1-8
  16. Drazic A.*, Aksnes H.*, Marie M.*, Boczkowska M., Varland S., Timmerman E., Foyn H., Glomnes N., Rebowski G., Impens F., Gevaert K., Dominguez R., Arnesen T. (2018) NAA80 is actin’s N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility. Proc Natl Acad Sci USA 115: 4399-4404
  17. Goris M., Magin R.S., Foyn H., Myklebust L.M., Varland S., Ree R., Drazic A., Bhambra P., Støve S.I., Baumann M., Haug B.E., Marmorstein R., Arnesen T. (2018) Structural determinants and cellular environment define processed actin as the sole substrate of the N-terminal acetyltransferase NAA80. Proc Natl Acad Sci USA 115: 4405-4410
  18. Aksnes H., Marie M., Arnesen T., Drazic A. (2018) Actin polymerization and cell motility are affected by NAA80-mediated posttranslational N-terminal acetylation of actin. Communicative & Integrative Biology 11: e1526572
  19. Varland S., Vandekerckhove J., Drazic A. (2018) Actin Posttranslational Modifications: Cinderella of Cytoskeletal Control. Trends Biochem Sci, accepted

Publications in national current research information system (CRIStin)

2018 Proteomics Data Analysis Workshop

Bergen, Norway (MaxQuant by Jürgen Cox; PeptideShaker by Harald Barsnes)

2018 14th MIC Confocal Microscopey Course

Department of Biomedicine, University of Bergen, Norway

2017 Research stay

Prof. Roberto Dominguez, Department of Physiology, University of Pennsylvania, USA

2015-2017 PostDoc

Fellowship Deutsche Forschungsgemeinschaft (DFG), Prof. T. Arnesen, Department of Molecular Biology, University of Bergen, Norway

2014 Research fellow

Dr. K. Richter, Department of Chemistry, Technische Universität München, Germany

2011 Research stay

Prof. J.A. Imlay, Department of Microbiology, University of Illinois, USA

Education

2010-2013 Doctor rerum natiralium (Dr.rer.nat)

Title: Characterizion of the hypochlorite-specific transcription factor HypT and the effect of HOCl on the metabolism of E. coli

Supervisors: Dr. J. Winter and Prof. J. Buchner, Technsiche Universität München, Germany

2008-2010 M.Sc. in Biochemistry

Title: Characterisation of the transcription factor YjiE

Supervisors: Dr. J. Winter and Prof. J. Buchner, Technsiche Universität München, Germany

2005-2008 B.Sc. in Biochemistry

Title: The examination of a mutant of the peptide transporter PepT1

Supervisors: Dr. G. Kottra and Prof. H. Daniel, Technsiche Universität München, Germany

Investigation of the functional role of actin N-terminal modificataions

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