It is still unknown why this misfolding occurs. The first stages of folding and the onset of the aggregation of the proteins, the so-called oligomerisation, appear to be decisive for pathogenesis.
The Research teams of Prof. Klaus Gerwert and Prof. Detlev Riesner in Bochum and Düsseldorf have now been able to observe the proteins in their natural environment. They investigated the structural changes of the prion protein (PrP), the trigger for Creutzfeldt-Jacob Disease, by anchoring it to a cell membrane. As summarized by Prof. Gerwert, “Much to our surprise, the reaction of a membrane-anchored prion protein differs from that of a PrP in solution.
Unstructured parts of the protein fold in a manner that makes it easy for another prion protein to be adsorbed – the possible onset of the pathogenetic structure.” The results of this research work are available online in the current edition of the Proceedings of the National Academy of Science (PNAS).
Abnormal folding in replication
The prion protein is physiologically well-folded in a healthy organism, particularly within the central nervous system. If prion proteins refold, they can change into abnormally structured, infectious prion proteins. Insoluble deposits within the cells, so-called amyloid structures, which ultimately lead to the dissolution of the affected cells, gradually develop. Amyloid diseases are almost always fatal.
The binding of membranes changes the behaviour of the prions
Gerwert and Riesner are the first scientists who have been able to reproduce the situation in living cells by analyzing membrane-anchored prion proteins. They were surprised to discover that there is a difference between the behaviour of the membrane-anchored protein at the membrane and the un-bound membrane in solution, which had been the focal point of all biophysical research work to date.
The Nobel Prize Winner Kurt Wüthrich had also determined the three-dimensional structure of the prion protein on unanchored prion proteins. To cite Prof. Gerwert, “High concentrations of prion protein at the membrane result in unstructured parts of the prion protein folding in a manner that makes it easy for numerous prion proteins to be adsorbed.
So-called beta sheets, comparable with two corrugated iron sheets, develop, enabling easy and perfectly fitting anchorage of the proteins.” The folding thus appears to induce the oligomerisation and possibly also the pathogenetic structure. To date, the structure of fully glycosylated prion proteins at the membrane has not been described in research reports.
Infrared spectroscopy identifies the folding
This new information could be gained by interdisciplinary cooperation of the two research teams. The team from Düsseldorf has already presented many important reports on prion research in the past. The studies on the folding of the membranes were then performed in Bochum. A new method was introduced: the prion protein was anchored to a membrane that was placed on an ATR (attenuated total reflectance) crystal.
The folding was then analyzed by infrared spectroscopy. “If an infrared ray passes through the ATR crystal, part of the radiation penetrates into and is absorbed by the attached sample,” explained Prof. Gerwert. “The absorption is just as unique for a protein structure as a fingerprint is for a human being.” In the infrared spectrum, every protein structure creates its own pattern. Changes therein are direct signs of a folding procedure.
Prof. Dr. Klaus Gerwert | alfa
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences