Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

German and Israeli Scientists Gain New Insights into Protein Disposal

27.05.2013
Cells have a sophisticated system to control and dispose of defective, superfluous proteins and thus to prevent damage to the body.

Researchers of the Max Delbrück Center (MDC), Germany, and the Technion, the Technical University of Israel in Haifa, have now discovered a new function of an enzyme that is involved in this vital process. Using yeast cells as a model organism, the researchers showed that a specific factor, abbreviated Cue1, is not only a receptor and activator for a component of the degradation apparatus, but also contributes to ensuring that the defective protein is marked with a molecular tag for degradation (Molecular Cell, doi: org/10.1016/j.molcel.2013.04.005)*.

Proteins are molecular machines in the cells of an organism. Different types of proteins perform many different functions: They transport materials to their destination, ward off pathogens, enable chemical reactions in the cell and much more. Many proteins are produced in a cell organelle, the endoplasmic reticulum (ER), are then folded and subsequently transported to their destination.

Some proteins are only required for a specific, time-limited purpose and must be degraded once their purpose has been served. But errors also frequently occur during production and folding. These defective proteins are not functional and can even harm the organism. Therefore they, too, must be degraded.

The cells therefore have a sophisticated system to dispose of defective, superfluous proteins. In the ER there is a special process for protein degradation, known as ER-associated degradation (ERAD). This system contains a number of enzymes that cooperate to ensure that a defective protein is marked with a molecular tag, the molecule ubiquitin. This process is called ubiquitylation. A chain of four to six molecules serves as degradation signal. A protein tagged with such a molecular chain is transported to the proteasome, the protein-cleaving machinery of the cell, where it is separated into its components.

This ubiquitin-proteasome system is found in all eukaryotic cells; it is ubiquitous. It is one of the most complex cellular systems and protects the body from severe diseases. Defective proteins that escape this system trigger serious diseases such as Alzheimer’s, Parkinson’s, Huntington’s disease, cystic fibrosis or diabetes. The scientist who discovered this protective program is Professor Aaron Ciechanover of Technion, the Technical University of Israel in Haifa. He received the Nobel Prize in Chemistry in 2004 for this achievement together with Professor Avram Hershko (Technion) and Professor Irwin Rose (University of California, Irvine, USA).

Several enzymes must work in concert to facilitate the attachment of a ubiquitin chain to a defective protein. Some of these enzymes are anchored in the membrane of the ER, others such as the enzyme Ubc7 swim freely inside the cell. A factor called CUE1, which itself is bound to the membrane, is responsible for recruiting Ubc7 and escorting it to the enzymes at the membrane. To achieve this, it has a domain which binds specifically to Ubc7. Another domain of the factor is the so-called CUE domain. Dr. Katrin Bagola and Professor Thomas Sommer of the MDC have studied its function in yeast cells together with their colleagues Professor Michael Glickman (Technion) and Professor Ciechanover.

Fateful connection
The CUE domain is a ubiquitin-binding domain (UBD). UBDs bind to specific ubiquitin patterns. For example, they can recognize whether one or more ubiquitin molecules have been attached to a protein and how the respective ubiquitin molecules are linked together in chains. The ubiquitin pattern determines which ubiquitin domain binds to which protein and thus determines the subsequent fate of the protein.
Direct impact on molecular chain formation – Signal for protein degradation
The MDC and Technion researchers, who have collaborated closely for many years, showed that the CUE domain of the factor Cue1 binds to ubiquitin chains that are linked together via a specific building block of the individual ubiquitin molecules. These chains subsequently serve as a degradation signal for proteins. In addition, the researchers found that the CUE domain also has a direct impact on the length of the ubiquitin chains: If the CUE domain was lacking or limited in its function due to a mutation, the ubiquitin chains developed more slowly and were shorter in length. Apparently, the CUE domain stabilizes the ubiquitin chains, allowing additional ubiquitin molecules to be attached more easily.

In yeast cells, the researchers found that the CUE domain of Cue1 in this way actually affects how effectively the ERAD system can degrade proteins. The researchers suspect that the CUE domain is used specifically for the disposal of proteins which are bound to the ER membrane. However, they seem to have no influence on the degradation of soluble proteins. “Our results show that a ubiquitin-binding domain can also regulate the formation of ubiquitin chains,” the researchers said. “This function was previously unknown until now.”

* Ubiquitin binding by a CUE domain regulates ubiquitin chain formation by ERAD E3 ligases.
Katrin Bagola1, Maximilian von Delbrück1, Gunnar Dittmar1, Martin Scheffner3, Inbal Ziv4, Michael H. Glickman4, Aaron Ciechanover5, and Thomas Sommer1, 2

1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13122 Berlin, Germany
2Humboldt-University zu Berlin, Institute for Biology, Invalidenstr.43, D-10115 Berlin, Germany
3Department of Biology, Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany
4Department of Biology and 5Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Polak Cancer Center, Technion-Israel Institute of Technology, Haifa 31096, Israel

Contact:
Barbara Bachtler
Press Department
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
in the Helmholtz Association
Robert-Rössle-Strasse 10; 13125 Berlin, Germany
Phone: +49 (0) 30 94 06 - 38 96; Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de

Barbara Bachtler | Max-Delbrück-Centrum
Further information:
http://www.mdc-berlin.de/

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Lightning, with a chance of antimatter

24.11.2017 | Earth Sciences

A huge hydrogen generator at the Earth's core-mantle boundary

24.11.2017 | Earth Sciences

Scientists find why CP El Niño is harder to predict than EP El Niño

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>