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
Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory
‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden
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,...
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...
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...
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...
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...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
11.12.2017 | Physics and Astronomy
11.12.2017 | Earth Sciences
11.12.2017 | Information Technology