Developed by Zhihao Zhuang, UD assistant professor of chemistry and biochemistry, and his research group, the chemical method yields hundredsfold more ubiquitylated proteins than current approaches. Such proteins may hold the key to revealing such mysteries as how cancer cells gain resistance to cancer drugs.
The advance is reported in the April issue of Nature Chemical Biology, the leading journal in the field of chemical biology. Zhuang's co-authors include graduate students Junjun Chen and Jialiang Wang and postdoctoral fellow Yongxing Ai, all from UD, and Lajos Haracska, a researcher in the Institute of Genetics at the Hungarian Academy of Sciences.
Ubiquitin is a small protein, the basis of Nobel Prize-winning research in 2004, which deemed the molecule the “kiss of death” for its role in tagging damaged or unneeded proteins for the cell's waste disposal in the constant process of protein generation and degradation. In recent years, the non-proteolytic functions of ubiquitin in diverse cellular processes, including protein trafficking, immune response, and DNA damage tolerance, have been discovered at a rapid pace, and it has become clear that ubiquitin plays far-broader roles in cell biology.
However, preparing sufficient samples of ubiquitylated proteins for study has been a major challenge facing scientists.
The availability of these proteins is critical for Zhuang and members of his research team, who are working at the interface of chemistry and biology trying to understand the molecular basis of human cancer development and prevention.
The new method for developing ubiquitylated proteins, which Zhuang and his team developed, combines the power of intein chemistry and disulfide crosslinking to bond ubiquitin to another essential protein called proliferating cell nuclear antigen.
“Our yield is hundredsfold higher compared to the commonly used enzymatic approach,” Zhuang says. “We also have the flexibility of modifying the selected residues, which has not been possible with the previous approach.”
In investigating the effect of the differently modified proteins, Zhuang and his group also revealed a surprising phenomenon regarding ubiquitylation.
“We found that ubiquitin as a protein modifier is far more flexible than we have thought. This property distinguishes ubiquitylation from other better studied protein post-translational modifications, such as phosphorylation and acetylation,” Zhuang says.
The new UD approach will help researchers studying ubiquitin biology by providing the means to prepare milligrams of protein samples for in-depth structural and functional characterization.
SInce the publication of the work online in Nature Chemical Biology, Zhuang has received requests for samples from research groups across the United States.
Additionally, the new approach has already opened up doors to new research in Zhuang's own laboratory, where he and his team are investigating new anti-cancer therapies.
The research on the new method was supported by Zhuang's laboratory start-up funding from UD, as well as a recent grant from the University of Delaware Research Foundation (UDRF).
Tracey Bryant | Newswise Science News
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine