Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein aggregation: Assemblies of proteins relevant not only for Alzheimer’s and Parkinson’s disease

21.08.2019

Publication in Nature Communications

Amyloid fibrils play a crucial role in neurodegenerative illnesses. Scientists from Heinrich Heine University Düsseldorf (HHU) and Forschungszentrum Jülich have now been able to use cryo-electron microscopy (cryo-EM) to decode the spatial structure of the fibrils that are formed from PI3K SH3 domains – an important model system for research. Although the fibrils examined are not themselves connected with an illness, the findings made and methods developed could serve to understand diseases such as Alzheimer’s and Parkinson’s.


Cross section of the 3D model of an amyloid fibril against the backdrop of a cryo-electron microscopy recording. A PI3K SH3 domain is highlighted in yellow.

FZJ / Christine Röder

Proteins are central components of living material. These complex molecules made up of combinations of individual amino acids in some cases comprise thousands of individual atoms and have sophisticated three dimensional shapes. The term ‘fold’ is used to describe this structure. The fold of a protein determines its biological function.

Misfolding into non-natural structures and associated aggregation makes proteins not only useless but potentially toxic. The current view is that many neurodegenerative diseases are triggered by misfolded proteins. They form deposits in critical parts of the central nervous system. Initially, fibrillar structures, referred to as ‘amyloid fibrils’, form. Larger deposits of such amyloid fibrils form the typical plaques that can be found in the brain tissue and can restrict, damage or kill nerve cells.

The PI3K SH3 domains are usually part of larger proteins, but can also exist alone in their correctly folded form. They play a major role in cellular communication. For many years, these domains have been used as model systems in order to examine protein folding and thus determine the causes of misfolding.

This is because researchers have discovered that these domains can also form amyloid fibrils that do not differ from the fibrils typical for diseases and are just as poisonous to cells. In fact, all proteins can potentially form amyloid fibrils; healthy organisms must actively and constantly combat this process.

Many fundamental discoveries of amyloid fibrils that are directly applicable to disease-related proteins were made using this model system. “But what we didn’t know until now was the precise three-dimensional structure of the fibrils from the PI3K SH3 domains,” explains Prof. Dr. Gunnar Schröder, Professor of Computational Structural Biology at HHU as well as work group leader at Forschungszentrum Jülich.

“Now we can use cryo-EM to understand these structures fully,” adds Prof. Dr. Alexander Büll, corresponding author alongside Schröder of the study published in Nature Communications. Büll was an Assistant Professor at HHU until early 2019 and is now a Full Professor in the Department of Biotechnology and Biomedicine at the Technical University of Denmark in Lyngby. Speaking about the significance of this determined structure, Prof. Schröder adds: “Now that we know the spatial structure, much of the earlier data from the last 20 years can be reinterpreted or interpreted more quantitatively.”

“Cryo-electron microscopy is a wonderful tool for determining the three-dimensional structure of the fibrils,” emphasises Christine Röder, first author of the study and a member of Prof. Schröder’s work group in Jülich. The 2017 Nobel Prize in Chemistry was awarded for the development of this method, with which complex biomolecules that adopt their natural form only in an aqueous environment can be presented in atomic resolution.

The samples dissolved in water – for example proteins – are plunge-frozen to very low temperatures and thus fixed in their natural structure. This makes it possible to examine them under an electron microscope in this state. However, this can’t be achieved with a single image, but in a succession of several recordings that show the protein from different angles. Computers then put the many individual recordings together to form a three-dimensional image.

Originalpublikation:

Christine Röder, Nicola Vettore, Lena N. Mangels, Lothar Gremer, Raimond B. G. Ravelli, Dieter Willbold, Wolfgang Hoyer, Alexander K. Buell & Gunnar F. Schröder, Atomic structure of PI3-kinase SH3 amyloid fibrils by cryo-electron microscopy, Nature Communications (2019) 10:3754
DOI: 10.1038/s41467-019-11320-8

Weitere Informationen:

https://rdcu.be/bPb4C

Dr.rer.nat. Arne Claussen | idw - Informationsdienst Wissenschaft
Further information:
http://www.hhu.de/

More articles from Life Sciences:

nachricht Turning carbon dioxide into liquid fuel
06.08.2020 | DOE/Argonne National Laboratory

nachricht Tellurium makes the difference
06.08.2020 | Friedrich-Schiller-Universität Jena

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: ScanCut project completed: laser cutting enables more intricate plug connector designs

Scientists at the Fraunhofer Institute for Laser Technology ILT have come up with a striking new addition to contact stamping technologies in the ERDF research project ScanCut. In collaboration with industry partners from North Rhine-Westphalia, the Aachen-based team of researchers developed a hybrid manufacturing process for the laser cutting of thin-walled metal strips. This new process makes it possible to fabricate even the tiniest details of contact parts in an eco-friendly, high-precision and efficient manner.

Plug connectors are tiny and, at first glance, unremarkable – yet modern vehicles would be unable to function without them. Several thousand plug connectors...

Im Focus: New Strategy Against Osteoporosis

An international research team has found a new approach that may be able to reduce bone loss in osteoporosis and maintain bone health.

Osteoporosis is the most common age-related bone disease which affects hundreds of millions of individuals worldwide. It is estimated that one in three women...

Im Focus: AI & single-cell genomics

New software predicts cell fate

Traditional single-cell sequencing methods help to reveal insights about cellular differences and functions - but they do this with static snapshots only...

Im Focus: TU Graz Researchers synthesize nanoparticles tailored for special applications

“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.

Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...

Im Focus: Tailored light inspired by nature

An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.

Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“Conference on Laser Polishing – LaP 2020”: The final touches for surfaces

23.07.2020 | Event News

Conference radar for cybersecurity

21.07.2020 | Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

 
Latest News

Rare Earth Elements in Norwegian Fjords?

06.08.2020 | Earth Sciences

Anode material for safe batteries with a long cycle life

06.08.2020 | Power and Electrical Engineering

Turning carbon dioxide into liquid fuel

06.08.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>