Chaperone proteins in human cells dynamically interact with the protein α-Synuclein, which is strongly associated with Parkinson’s disease. A disturbed relationship to these “bodyguards” leads to cell damage and the formation of Lewy bodies typical for Parkinson’s disease. The findings by researchers from the University of Basel’s Biozentrum have been published in “Nature”.
Parkinson’s disease is one of the most common neurodegenerative disorders. In Switzerland, about 15,000 people are affected. Because of the worldwide rise in life expectancy, a rapid increase in Parkinson’s cases is expected in the next years.
The causes of the disease, which leads to the progressive death of nerve cells in the brain, are still not well understood. Therefore, the development of effective therapies is all the more difficult.
It is well accepted that the protein α-Synuclein can play a key role in the development of Parkinson’s. Researchers led by structural biologist Prof. Sebastian Hiller have now discovered that assisting proteins, known as chaperones, are constantly protecting α-Synuclein in human cells. Whenever the chaperones are unable to fulfill their bodyguard job, α-Synuclein shows its negative side and causes serious cell damage.
Molecular bodyguards interact with α-Synuclein
In human cells, there are about thirty to forty chaperones that can potentially interact with α-Synuclein. The scientists have systematically investigated at the atomic level where the molecular bodyguards interact with α-Synuclein.
“Using state-of-the-art NMR technology, we have discovered a specific pattern that determines the exact interaction site of α-Synuclein with chaperones,” explains Hiller. “There is not fixed, rigid interaction, but a dynamic and constantly changing encounter.” In healthy cells, α-Synuclein is always accompanied by chaperones such that the protein remains transportable and at all times a pool of functional α-Synuclein proteins is available.
Impaired chaperone binding causes cell damage
There are serious consequences if the chaperones are no longer able to perform their bodyguard function. Chemical modifications of α-Synuclein, such as those observed in Parkinson’s disease, interfere with chaperone binding. These “unaccompanied” α-Synuclein proteins can re-localize and accumulate on the membrane of mitochondria, the power plants of the cell, and gradually destroy them. As recently shown, Lewy bodies typical for Parkinson’s disease mainly consist of mitochondrial membrane fragments and α-Synuclein.
New function for chaperones discovered
“With our work, we are questioning the paradigm that the function of chaperones is solely to help proteins to fold into their proper shape,” says Hiller. “Chaperones do far more than just assist in protein folding. They control cellular processes by flexibly interacting with a variety of proteins and accompanying them like a shadow.”
Understanding the molecular interactions and the interactions between the partners involved provides important clues for the treatment of Parkinson’s disease. In the future, chaperones and the maintenance of their function should also be considered in the development of novel therapies.
Prof. Dr. Sebastian Hiller, University of Basel, Biozentrum, tel. +41 61 207 20 82, email: email@example.com
Björn M. Burmann, Juan A. Gerez, Irena Matečko-Burmann, Silvia Campioni, Pratibha Kumari, Dhiman Ghosh, Adam Mazur, Emelie E. Aspholm, Darius Šulskis, Magdalena Wawrzyniuk, Thomas Bock, Alexander Schmidt, Stefan G.D. Rüdiger, Roland Riek, Sebastian Hiller
α-Synuclein regulation by chaperones in mammalian cells
Nature (2019), doi: 10.1038/s41586-019-1808-9
Dr. Katrin Bühler | Universität Basel
New self-assembled monolayer is resistant to air
22.01.2020 | University of Groningen
Mosquitoes are drawn to flowers as much as people -- and now scientists know why
22.01.2020 | University of Washington
A Duke University research team has identified a new function of a gene called huntingtin, a mutation of which underlies the progressive neurodegenerative...
For years, a new synthesis method has been developed at TU Wien (Vienna) to unlock the secrets of "strange metals". Now a breakthrough has been achieved. The results have been published in "Science".
Superconductors allow electrical current to flow without any resistance - but only below a certain critical temperature. Many materials have to be cooled down...
KIT researchers develop novel composites of DNA, silica particles, and carbon nanotubes -- Properties can be tailored to various applications
Using DNA, smallest silica particles, and carbon nanotubes, researchers of Karlsruhe Institute of Technology (KIT) developed novel programmable materials....
Styrofoam or copper - both materials have very different properties with regard to their ability to conduct heat. Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz and the University of Bayreuth have now jointly developed and characterized a novel, extremely thin and transparent material that has different thermal conduction properties depending on the direction. While it can conduct heat extremely well in one direction, it shows good thermal insulation in the other direction.
Thermal insulation and thermal conduction play a crucial role in our everyday lives - from computer processors, where it is important to dissipate heat as...
In order to advance the transfer of research developments from the field of quantum sensor technology into industrial applications, an application laboratory is being established at Fraunhofer IAF. This will enable interested companies and especially regional SMEs and start-ups to evaluate the innovation potential of quantum sensors for their specific requirements. Both the state of Baden-Württemberg and the Fraunhofer-Gesellschaft are supporting the four-year project with one million euros each.
The application laboratory is being set up as part of the Fraunhofer lighthouse project »QMag«, short for quantum magnetometry. In this project, researchers...
16.01.2020 | Event News
15.01.2020 | Event News
07.01.2020 | Event News
22.01.2020 | Life Sciences
22.01.2020 | Power and Electrical Engineering
22.01.2020 | Life Sciences