Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tracing down linear ubiquitination

21.03.2017

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many different forms, either as single molecule or in the form of distinct ubiquitin chains, leading to diverse conformations and varying cellular outcomes. Scientists often refer to it as the secret ubiquitin code, which still needs to be fully deciphered.


Schematic model of two linearly linked ubiquitin molecules. The internal tagging site is marked in black.

Image by Koraljka Husnjak using PyMOL software.

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have now developed a novel technology to tackle that.

Recently, scientists discovered that ubiquitin molecules are not only assembled in a non-linear manner, but also build linear chains, in which the head of one ubiquitin is linked to the tail of another ubiquitin molecule. So far, only two highly specific enzymes are known capable of synthesizing and degrading such linear ubiquitin chains, and both are being extensively studied at the Institute of Biochemistry II at the Goethe University Frankfurt.

However, target proteins of linear ubiquitination, as well as their specific cellular functions, have largely remained elusive. The novel technology developed by the team around Koraljka Husnjak from the Goethe University Frankfurt now enables the systematic analysis of linear ubiquitination targets.

“The slow progress in this research area was mainly due to the lack of suitable methods for proteomic analysis of proteins modified with linear ubiquitin chains”, explains Koraljka Husnjak whose native country is Croatia. Her team solved the problem by internally modifying the ubiquitin molecule in such a way that it maintains its cellular functions whilst at the same time enabling the enrichment and further analysis of linear ubiquitin targets by mass spectrometry.

With this technology at hand, it is now possible to identify target proteins modified by linear ubiquitin, and to detect the exact position within the protein where the linear chain is attached. Scientists praise this highly sensitive approach as an important breakthrough that will strongly improve our understanding of the functions of linear ubiquitination and its role in diseases.

Dr. Husnjak already provided the proof of this concept and identified several novel proteins modified by linear ubiquitin chains. Amongst them are essential components of one of the major pro-inflammatory pathways within cells. “Linear ubiquitin chains relay signals that play an important role in the regulation of immune responses, in pathogen defence and immunological disorders. Until now we know very little about how small slips in this system contribute to severe diseases, and how we can manipulate it for therapeutic purposes” comments Husnjak the potential of the new technology.

Errors in the ubiquitin system have been linked to numerous diseases including cancer and neurodegenerative disorders such as Parkinson’s disease, but also to the development and progression of infections and inflammatory diseases.

Publication:
Katarzyna Kliza, Christoph Taumer, Irene Pinzuti, Mirita Franz-Wachtel, Simone Kunzelmann, Benjamin Stieglitz, Boris Macek & Koraljka Husnjak. Internally tagged ubiquitin: a tool to identify linear polyubiquitin-modified proteins by mass spectrometry. Nature Methods 2017. doi:10.1038/nmeth.4228

Information: Dr. Koraljka Husnjak, Institut für Biochemie II, Fachbereich 16, Universitätsklinikum Frankfurt, Tel.: (069) 6301 5820, k.husnjak@biochem2.uni-frankfurt.de.

Goethe University is a research-oriented university in the European financial centre Frankfurt The university was founded in 1914 through private funding, primarily from Jewish sponsors, and has since produced pioneering achievements in the areas of social sciences, sociology and economics, medicine, quantum physics, brain research, and labour law. It gained a unique level of autonomy on 1 January 2008 by returning to its historic roots as a "foundation university". Today, it is among the top ten in external funding and among the top three largest universities in Germany, with three clusters of excellence in medicine, life sciences and the humanities. Together with the Technical University of Darmstadt and the University of Mainz, it acts as a partner of the inter-state strategic Rhine-Main University Alliance.
Current news about science, teaching, and society in GOETHE-UNI online (www.aktuelles.uni-frankfurt.de)

Publisher: The President of Goethe University
Editor: Dr. Anne Hardy, Press Information Officer, Phone: +49(0)69 798-12498, Fax +49(0)69 798-761 12531, hardy@pvw.uni-frankfurt.de
Internet: www.uni-frankfurt.de

Dr. Anne Hardy | idw - Informationsdienst Wissenschaft

Further reports about: Tracing cellular functions proteins ubiquitin molecule ubiquitination

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

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...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

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...

Im Focus: Breaking the bond: To take part or not?

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...

Im Focus: New 2D Spectroscopy Methods

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....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Global study of world's beaches shows threat to protected areas

19.07.2018 | Earth Sciences

New creepy, crawly search and rescue robot developed at Ben-Gurion U

19.07.2018 | Power and Electrical Engineering

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>