Human proteins undergo a variety of chemical modifications following their synthesis. These modifications regulate their structure, function, and stability. Researchers from the Bhogaraju Group at EMBL Grenoble have developed a new method to study a critical type of protein modification process called ubiquitination.
Ubiquitination plays an integral role in diverse cellular functions, and its dysregulation contributes to many human diseases, including neurodegeneration and cancer. During ubiquitination, a group of enzymes called E3 ubiquitin ligases attach a small protein called ubiquitin to other proteins. This tagging, in turn, helps determine the fate of the targeted protein.
Ubiquitination is highly pervasive in humans and it is estimated that every human protein undergoes ubiquitination at least once in its lifetime. The diversity of cellular functions of ubiquitination is reflected in the existence of over 600 human E3 ligase genes, representing ~3% of the human genome. Mapping the human E3 target protein landscape can help us understand their function and eventually target them for therapeutics.
However, a significant number of E3 ligases and their targets remain poorly characterised, one of the reasons being the extremely transient nature of their interaction. Current methods for mapping such interactions are also highly resource-intensive, which limits their use and scalability. To solve this problem, the Bhogaraju Group, which investigates ubiquitination pathways in.