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

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

Ultrathin device harvests electricity from human motion

24.07.2017 | Power and Electrical Engineering

Scientists announce the quest for high-index materials

24.07.2017 | Materials Sciences

ADIR Project: Lasers Recover Valuable Materials

24.07.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>