This precarious stability leaves proteins and the living beings that depend upon them on the edge of a precipice, where a single destabilizing change in a key protein can lead to disease or death. It also greatly complicates the manufacture and use of proteins in research and medicine.
Finding a way to stabilize proteins could help prevent such dire consequences, reduce the very high cost of protein drugs and perhaps also help scientists understand why proteins are often so unstable in the first place. In a paper published in the Dec. 11 issue of the journal Molecular Cell, researchers at the University of Michigan and the University of Leeds describe a new strategy for stabilizing specific proteins by directly linking their stability to the antibiotic resistance of bacteria.
"The method we developed should provide an easy way to strengthen many proteins and by doing so increase their practical utility," said James Bardwell, a Howard Hughes Medical Institute investigator and professor of molecular, cellular and developmental biology at U-M.
In the new approach, the researchers found that when a protein is inserted into the middle of an antibiotic resistance marker, bacterial antibiotic resistance becomes dependent upon how stable the inserted protein is. This enabled the scientists to easily select for stabilizing mutations in proteins by using a simple life-or-death test for bacterial growth on antibiotics. The mutations the scientists identified rendered proteins more resistant to unfolding.
"This method also has allowed us to catch a glimpse of why proteins may need to be just barely stable," said Linda Foit, the graduate student at U-M who initiated the work. "The mutations that we found to enhance the stability of our model protein are mostly in key areas related to the protein's function, suggesting that this protein may need to be flexible and therefore marginally stable in order to work. It may be that, over the course of evolution, natural selection acts to optimize, rather than maximize protein stability."
The work was conducted in the laboratories of Bardwell at U-M and Sheena Radford at the University of Leeds and spearheaded by Foit in Bardwell's lab and postdoctoral fellow Gareth Morgan in the Radford lab. In addition to these researchers, the paper's authors are U-M undergraduate students Maximilian Kern, Lenz Steimer and Anne Kathrin von Hacht and Leeds technician James Titchmarsh and senior lecturer Stuart Warriner. The research was funded in part by the Howard Hughes Medical Institute, the National Institutes of Health, the Wellcome Trust and the University of Leeds.
For more information:
James Bardwell: http://www.ns.umich.edu/htdocs/public/experts/ExpDisplay.php?beginswith=Bardwell
Molecular Cell: http://www.cell.com/molecular-cell/home
Nancy Ross-Flanigan | Newswise Science News
For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)
New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
27.06.2017 | Power and Electrical Engineering
27.06.2017 | Information Technology
27.06.2017 | Physics and Astronomy