Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First atomic-level look at a protein that causes brain disease

24.04.2008
For the first time, researchers have peered deeply at the atomic level into the protein that causes hereditary cerebral amyloid angiopathy (CAA) -- a disease thought to cause stroke and dementia.

The study pinpointed a tiny portion of the protein molecule that is key to the formation of plaques in blood vessels in the brain.

Ohio State University chemist Christopher Jaroniec and his colleagues report their results this week in the online edition of the Proceedings of the National Academy of Sciences.

Researchers worldwide are working to understand how certain kinds of proteins, called prions, cause degenerative brain diseases such as CAA. More common prion diseases include bovine spongiform encephalopathy (mad cow disease), and Creutzfeldt-Jakob disease in humans. All are incurable and fatal.

Jaroniec understands that any discovery related to prions could raise people’s hopes for a cure, but he emphasized that his study is only a first step towards understanding the structure of the prion for CAA.

“This is a very basic study of the structure of the protein, and hopefully it will give other researchers the information they need to perform further studies, and improve our understanding of CAA,” he said.

His team partnered with biochemists from Case Western Reserve University, who took a fragment of the human prion protein for CAA and tagged it with chemical markers.

Jaroniec explained that, while the prion protein used in the study is associated with the development of hereditary CAA, it is not infectious.

After the researchers tagged the molecule, they created the right chemical conditions for it to fold into macromolecules called amyloid fibrils.

Researchers know that in the body, these fibrils form plaques that lodge in blood vessel walls in the brain. But nobody has been able to closely examine the molecular structure of CAA fibrils until now.

“These fibrils are very large and complex, and so traditional biochemical techniques won’t reveal their structure in detail,” Jaroniec said.

The assistant professor of chemistry at Ohio State is an expert in a technique that can reveal the structure of such large molecules: solid-state nuclear magnetic resonance (NMR) spectroscopy.

NMR works by tuning into the radio waves emitted by atoms within materials. Every atom emits radio waves at a particular frequency, depending on the types of atoms that surround it.

The NMR technique the chemists used, called “magic angle spinning,” involves spinning materials at a certain angle with respect to the NMR's magnetic field in order to remove radio interference among the atoms. It offers researchers a clear view of which atoms make up a particular molecule, and how those atoms are arranged.

So after the researchers let the prion proteins fold into amyloid fibrils, they used magic angle spinning NMR to study the fibrils’ structure.

They searched the NMR signals for the chemical tags that had been planted in the prions. In that way, they were able to determine what parts of the original prion protein were contained within the fibrils.

They found, to their surprise, that some 80 percent of the original prion protein molecule was not present in the fibrils. The fibrils consisted exclusively of the remaining 20 percent -- approximately 29 amino acids, of which two appear to be especially critical to the structure of the molecule.

Other studies have suggested that these two amino acids, numbered 138 and 139, were key to the formation of the CAA fibrils, Jaroniec said. But this study is the first to confirm their importance by studying them at the atomic level.

The researchers are continuing this work, and plan to examine the structure of the fibrils in more detail, as well as other strains of the CAA prion protein.

Jaroniec’s partners on this project included Jonathan Helmus and Philippe Naudaud, both doctoral students at Ohio State, and their collaborators at Case Western.

This research was funded by Ohio State University and the National Institutes of Health.

Christopher Jaroniec | EurekAlert!
Further information:
http://www.osu.edu

More articles from Studies and Analyses:

nachricht Amputees can learn to control a robotic arm with their minds
28.11.2017 | University of Chicago Medical Center

nachricht The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

Im Focus: Virtual Reality for Bacteria

An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications

Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...

Im Focus: A space-time sensor for light-matter interactions

Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.

The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Midwife and signpost for photons

11.12.2017 | Physics and Astronomy

How do megacities impact coastal seas? Searching for evidence in Chinese marginal seas

11.12.2017 | Earth Sciences

PhoxTroT: Optical Interconnect Technologies Revolutionized Data Centers and HPC Systems

11.12.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>