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Proteomics technique furthers understanding of ubiquitin signaling

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A new proteomics technique, termed ubiquitin clipping, has been developed to enable the production of high-definition maps detailing how proteins are modified by ubiquitination. Ubiquitin is a small protein that can link to other cellular proteins impacting cellular processes. The high-definition maps created from this technique enable subtle changes to be determined that ultimately contribute to a range of diseases including neurodegenerative disorders and cancer.

The research, published in Nature, details how ubiquitin clipping can map protein ubiquitination and modifications of cellular proteins that can impact their function. The technique, developed by Professor Komander (Walter and Eliza Hall Institute, Australia) and researchers from the University of Cambridge (UK) and the University of Vienna (Austria), pretreats protein samples and then analyzes them using electrophoresis and mass spectrometry.

“Ubiquitin clipping has enabled us to reveal a whole new level of complexity in ubiquitin signaling. In our pilot experiments, we discovered branched ubiquitin chains are much more common than previously thought. We could also study combinations of modifications on ubiquitin and other proteins—a feat that was until now rather difficult,” commented Professor Komander.

It is hoped that this new technique will identify ubiquitin patterns associated with diseases such as rheumatoid arthritis. Professor Komander concluded: “This is a revolutionary technique that simplifies ubiquitin research, enabling a new level of detailed experimentation. It’s the difference between describing a house based solely on the number of walls, windows and doors it has, versus looking at the detailed architectural plans.”

Sources: Swatek KN, Usher JL, Kueck AF et al. Insights into ubiquitin chain architecture using Ub-clipping. Nature, doi: 10.1038/s41586-019-1482-y (2019)(Epub ahead of print); https://phys.org/news/2019-08-proteomics-technique-insights-ubiquitin.html

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