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!
Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology
Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences