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.
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!
WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf
First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
22.05.2018 | Life Sciences
22.05.2018 | Earth Sciences
22.05.2018 | Trade Fair News