Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Deadly Folding Mistake

16.08.2013
Molecular mechanism of prion protein oligomerization at atomic resolution

Mad cow disease and its cousin Creutzfeld-Jakob disease cause fatal spongy changes in brain tissue. Today, we know that these diseases are caused by prions, proteins that are folded incorrectly.



A team of German researchers have now been able to follow how the diseased proteins aggregate and “infect” healthy ones on the atomic scale. Their report appears in the journal Angewandte Chemie.

How can a disease that is caused by a protein instead of a virus or bacterium be contagious? It is clear that incorrectly folded prion proteins must be able to deform their correctly folded analogues and to change their spatial structure. They transfer their own incorrect shape to the healthy proteins.

Normally, these proteins exist as monomers that are mostly wound into an alpha helix. When incorrectly folded, the protein has many regions containing beta sheets, structures that resemble an accordion, and has a tendency to self-assemble into larger aggregates. These amyloids cannot be broken down and thus form deposits in the brain’s tissue.

How this process works in detail has now been clarified. Kai Schlepckow and Harald Schwalbe at the Goethe University Frankfurt am Main have successfully used time-resolved NMR spectroscopic studies to follow what is happening to every individual amino acid as the prion protein molecules aggregate—an extremely complex process.

Their most interesting revelation is that the aggregation occurs in two steps. First, oligomers are formed from five to eight units. In the second step, these aggregate further into molecules made of up to 40 units that form fibrous structures. The first oligomerizations initially affect proteins in a largely unfolded state. Certain regions of the protein stiffen as the oligomerization proceeds. Different regions of the protein participate in different phases of the aggregation.

The researchers hope to use their new understanding to better determine what role is played by the specific mutations in the prion protein that seem to fuel initiation of this process. This may also provide a starting point for the development of effective drugs.

About the Author
Dr. Harald Schwalbe is Professor of Chemistry at the Johann Wolfgang Goethe University Frankfurt, Germany. His area of research is the study of dynamic states and conformational changes of proteins and RNA. To perform his experiments he develops new NMR spectroscopic techniques in order to examine processes such as the incorrect folding of prion proteins with the highest possible time resolution.
Author: Harald Schwalbe, Johann Wolfgang Goethe-Universität, Frankfurt am Main (Germany), http://schwalbe.org.chemie.uni-frankfurt.de/contact
Title: Molecular Mechanism of Prion Protein Oligomerization at Atomic Resolution
Angewandte Chemie International Edition, Permalink to the article: http://dx.doi.org/10.1002/anie.201305184

Harald Schwalbe | Angewandte Chemie
Further information:
http://pressroom.angewandte.org

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>