Scientists discover substrates for targeted protein degradation
All life forms depend on proteins which are encoded by genes. Whereas the regulation of protein amounts and activities is analysed in many laboratories, the signals that lead to a regulated degradation of specific proteins are far less well understood.
A German team led by the Freiburg-based biologist Professor Ralf Reski has discovered substrates and interaction partners of the so-called N-end rule pathway of protein degradation in the moss Physcomitrella patens. The study is published in the journal “Molecular and Cellular Proteomics”.
From previous research it was evident that an enzyme called ATE flags proteins with the amino acid arginine and that these arginylated proteins are subsequently degraded by the proteasome. “In humans, mice and flies ATE function is essential. Without it, embryos die”, Reski says.
His team had previously discovered that the moss Physcomitrella patens is more robust, as loss of ATE function affects development and energy storage but does not result in moss plants dying. Although the N-end rule pathway of protein degradation was discovered in 1986, it was unclear which proteins are flagged by ATE in plants.
For their current study the team from the Plant Biotechnology department of the University of Freiburg co-operated with Professor Andreas Schlosser and his group from the Rudolf Virchow Center for Experimental Biomedicine of the University of Würzburg.
Together, they developed novel methods in immuno-precipitation and mass spectrometry of arginylated proteins and found five needles in the haystack: After analysing about thirty thousand protein spectra the scientists identified four specific proteins that are flagged by ATE and a small heat shock protein that may act as a molecular chaperone to support ATE function. “Our results provide mechanistic insights into the targeted protein degradation in plants”, Reski says. “They may also help to increase the production of human proteins in moss.” Recently, the first moss-made human protein received the approval of the German regulatory authority BfArM for clinical trials.
The biologists from Freiburg are specialists in moss research and have helped to develop Physcomitrella as a model organism for biology and biotechnology at a world-wide scale. Research was supported by the German Research Foundation DFG, the Freiburg Cluster of Excellence BIOSS Centre for Biological Signalling Studies and the Freiburg Institute for Advanced Studies FRIAS of the University of Freiburg.
Ralf Reski heads the Chair of Plant Biotechnology at the University of Freiburg. The biologist is a member of BIOSS and was Senior Fellow at FRIAS and at USIAS, the University of Strasbourg Institute for Advanced Study, France.
Sebastian N.W. Hoernstein, Stefanie J. Mueller, Kathrin Fiedler, Marc Schuelke, Jens T. Vanselow, Christian Schüssele, Daniel Lang, Roland Nitschke, Gabor L. Igloi, Andreas Schlosser, Ralf Reski (2016): Identification of targets and interaction partners of arginyl-tRNA protein transferase in the moss Physcomitrella patens. Molecular and Cellular Proteomics, DOI: 10.1074/mcp.M115.057190.
Professor Dr. Ralf Reski
Chair Plant Biotechnology
Faculty of Biology
University of Freiburg
Phone: +49 761 203 6968
Rudolf-Werner Dreier | Albert-Ludwigs-Universität Freiburg im Breisgau
World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
17.07.2018 | Information Technology
17.07.2018 | Materials Sciences
17.07.2018 | Power and Electrical Engineering