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
Bioluminescent sensor causes brain cells to glow in the dark
28.10.2016 | Vanderbilt University
Activation of 2 genes linked to development of atherosclerosis
28.10.2016 | Brigham and Women's Hospital
Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.
So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
28.10.2016 | Power and Electrical Engineering
28.10.2016 | Life Sciences
28.10.2016 | Life Sciences