Just as we humans do well to call the police or fire services in the event of an emergency, cells have helpers that are activated in a crisis. Cellular stress activates heat-shock transcription factor 1 (HSF1), which then binds DNA and facilitates the production of the cellular helpers. Researchers from the Max Planck Institute of Biochemistry in Martinsried have managed to demonstrate how this process works. Using X-ray crystallography, the scientists have decoded the exact structure of HSF1 and are thus able to explain the protein’s operating mode. Their work was recently published in the journal Nature Structural & Molecular Biology.
When there is an accident or a house fire, we call the police or the fire services. A control room quickly coordinates emergency operations.
The cells in our bodies also have helpers in a crisis; the heat-shock proteins. These are triggered in response to cellular stress, such as high temperature, UV radiation or cancer. Heat-shock proteins help other proteins maintain their functional structure and eliminate denatured proteins to counter the abnormal cellular situation.
In cells, the operator in the control room is HSF1, heat-shock transcription factor 1. It binds certain DNA sequences that encode the “assembly instructions” for the cellular helpers. When HSF1 is activated, the production of functional heat-shock proteins is triggered.
Andreas Bracher and his team in Prof. Hartl’s Department of Cellular Biochemistry at the Max Planck Institute of Biochemistry in Martinsried have demonstrated exactly how HSF1 binds DNA.
“Using X-ray crystallography, we studied the exact molecular arrangement,” explains Tobias Neudegger, a member of Bracher’s team and first author of the study. Proteins consist of long strands of amino acids which adopt a certain three-dimensional structure in order to become functionally active.
“We were able to show how three identical HSF1 molecules associate in case of cellular stress. That is how a stable DNA-HSF1 interaction occurs. If HSF1 is not bound to DNA, each individual HSF1 molecule is stored in an inactive state in the cell,” Neudegger explains.
The increased production of heat-shock proteins could be advantageous for the treatment of diseases. “Now that we know the HSF1 structure, drugs can be developed to activate or deactivate HSF1 and thus stimulate or inhibit the production of cellular helpers,” says Bracher, describing potential future HSF1 research.
Incorrectly folded proteins in the cells could be repaired or denatured proteins more easily eliminated. Incorrectly folded proteins are usually found in connection with Huntington’s disease, Alzheimer’s and Parkinson’s disease, as well as in cancer cells.
T. Neudegger, J. Verghese, M. Hayer-Hartl, F. U. Hartl & A. Bracher: Structure of human heat-shock transcription factor 1 in complex with DNA. Nature Structural & Molecular Biology, February 2016
Dr. Andreas Bracher
Department of Cellular Biochemistry
Max Planck Institute of Biochemistry
Am Klopferspitz 18
Dr. Christiane Menzfeld
Max Planck Institute of Biochemistry
Am Klopferspitz 18
Tel. +49 89 8578-2824
Dr. Christiane Menzfeld | Max-Planck-Institut für Biochemie
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction