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 | EurekAlert!
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
28.05.2018 | Event News
25.05.2018 | Event News
02.05.2018 | Event News
28.05.2018 | Seminars Workshops
28.05.2018 | Trade Fair News
28.05.2018 | Physics and Astronomy