When the prion protein misfolds and aggregates in humans, it can cause fatal neurodegenerative diseases such as Creutzfeldt-Jakob disease and Gerstmann–Sträussler–Scheinker syndrome.
These diseases have different symptoms, partly because the prion protein can misfold into different shapes. Just how a single protein can misfold into different aggregate conformations, however, has confounded scientists.
Now, Motomasa Tanaka and colleagues at the RIKEN Brain Science Institute in Wako have reported that small clusters of prion proteins called oligomers, which develop from monomer proteins, determine the eventual shape of the larger prion aggregate1. The findings were published in the journal Nature Chemical Biology in collaboration with researchers from the United States and from the RIKEN SPring-8 Center in Harima.
The research team used a yeast model system to study prion misfolding and aggregation, because yeast contain a prion-like protein called Sup35. This yeast protein misfolds into different aggregate conformations that cause the yeast to turn various colors—from white to pink—when they are grown on nutrient plates. A synthetic version of Sup35 can also form these distinct conformations when grown at different temperatures.
Using various biophysical techniques, the researchers observed that the synthetic Sup35 formed oligomers when they were grown at a low temperature, but not at a high temperature. The Sup35 grown at a low temperature made the yeast turn white, while Sup35 grown at a high temperature made the yeast turn pink. This suggests that the oligomers, formed at only the low temperature, may be an intermediate step in the formation of the larger aggregates that cause the ‘white’ phenotype.
The team then investigated which amino acid region of Sup35 is involved in the formation of the oligomer. By mutating various amino acids of the Sup35 protein, the researchers found that the parts of the protein required for oligomer formation were different to those required for creation of the larger aggregate. In addition, while oligomer formation was involved in acquisition of the ‘white’ phenotype, it was not required for driving the growth of the larger prion aggregate. These findings suggest that oligomers serve as an initial scaffold to determine the eventual shape—and therefore the physiological characteristics—of the larger prion aggregate. Tanaka proposes that “inhibiting these interactions between prion proteins could become a therapeutic strategy for the neurodegenerative prion diseases.”
The corresponding author for this highlight is based at the Tanaka Research Unit, RIKEN Brain Science Institute
Saeko Okada | Research asia research news
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences