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
Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia University
Researchers discover specific tumor environment that triggers cells to metastasize
22.11.2017 | University of California - San Diego
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
22.11.2017 | Life Sciences
22.11.2017 | Life Sciences
22.11.2017 | Materials Sciences