Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How cells degrade aberrant membrane proteins

13.07.2012
Heidelberg researchers unravel new degradation route

Researchers from Heidelberg University’s Center for Molecular Biology (ZMBH) have achieved unexpected insights into the process of how damaged proteins are degraded within cells. Their work focused on the function of a special protease.


In eukaryotic cells, misfolded membrane proteins are retained in the Endoplasmic Reticulum (ER) as assessed by immunofluorescence microscopy. The micrograph shows a damaged membrane protein in green and an ER-resident protein in red leading to various overlaps in yellow.
Image: ZMBH


The ER-resident rhomboid protease (blue) breaks up misfolded membrane proteins (green) within the membrane thereby initiating their transport to the cytosol and further degradation by the ubiquitin-proteasome system.
Image: ZMBH

This enzyme can hydrolyse peptide bonds in the plane of cellular membranes, a site where such water-requiring reactions commonly do not occur. The scientists working with Dr. Marius Lemberg could now show that this unusual protease recognises and degrades aberrant proteins directly in the membrane. The findings were published online in “Molecular Cell”.

When the research team around Dr. Lemberg started its work on a member of these special proteases they predicted by computational approaches that this enzyme would be active. However, they still faced the challenge to experimentally determine the physiological substrates. “The existing knowledge about relatives from the so-called rhomboid protease family did not help us in our quest for the molecules processed by the enzyme we discovered”, says Dr. Lemberg. Unlike all rhomboid proteases that had been studied so far, the new rhomboid localises to the Endoplasmic Reticulum (ER), the site in the cell where new membrane proteins are produced.

The breakthrough came after the researchers observed that the ER rhomboid protease is increasingly needed during protein folding stress. Proteins are produced as long chains of amino acids that have to correctly fold into a three-dimensional structure to fulfil their function. Especially when accumulating, misfolded proteins can severely damage cells and are known to cause impairments such as Alzheimer's and Parkinson's disease.

“We now have revealed that the ER rhomboid protease cleaves aberrant membrane proteins within their membrane anchor”, says Dr. Lemberg. Furthermore, the scientists demonstrated that this protease cooperates directly with components of the so-called ER-associated degradation (ERAD) pathway to dispose of the faulty protein. According to Dr. Lemberg, these new insights now provide the basis for a molecular understanding of how membrane proteins that make up a large fraction of cellular proteins are extracted from these membranes for degradation without getting into each other’s way.

The junior research group of Dr. Lemberg is part of the DKFZ-ZMBH Alliance – the strategic cooperation between the German Cancer Research Center (DKFZ) and the Heidelberg University's Center for Molecular Biology (ZMBH) – as well as of the interdisciplinary Network Aging Research (NAR) at Ruperto Carola. The group receives funding from the Baden-Württemberg Foundation.

For further information, go to: http://www.zmbh.uni-heidelberg.de/lemberg/default.shtml.

Original publication:
Lina Fleig, Nina Bergbold, Priyanka Sahasrabudhe, Beate Geiger, Lejla Kaltak, Marius K. Lemberg: Ubiquitin-Dependent Intramembrane Rhomboid Protease Promotes ERAD of Membrane Proteins. Mol. Cell (July 12, 2012), doi: 10.1016/j.molcel.2012.06.008.

Contact:
Dr. Marius Lemberg
Center for Molecular Biology of Heidelberg University (ZMBH)
DKFZ-ZMBH Alliance
Phone: +49 6221 54-5889 

m.lemberg@zmbh-heidelberg.de

Communications and Marketing
Press Office, phone: +49 6221 54-2311
pressestelle@rektorat.uni-heidelberg

Marietta Fuhrmann-Koch | idw
Further information:
http://www.zmbh.uni-heidelberg.de/lemberg/default.shtml
http://www.uni-heidelberg.de

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

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...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

NASA examines Peru's deadly rainfall

24.03.2017 | Earth Sciences

What does congenital Zika syndrome look like?

24.03.2017 | Health and Medicine

Steep rise of the Bernese Alps

24.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>