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
Tag it EASI – a new method for accurate protein analysis
19.06.2018 | Max-Planck-Institut für Biochemie
How to track and trace a protein: Nanosensors monitor intracellular deliveries
19.06.2018 | Universität Basel
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
19.06.2018 | Physics and Astronomy
19.06.2018 | Life Sciences
19.06.2018 | Physics and Astronomy