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
Cnidarians remotely control bacteria
21.09.2017 | Christian-Albrechts-Universität zu Kiel
Immune cells may heal bleeding brain after strokes
21.09.2017 | NIH/National Institute of Neurological Disorders and Stroke
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
21.09.2017 | Physics and Astronomy
21.09.2017 | Life Sciences
21.09.2017 | Health and Medicine