Chemical and Biological Strategies for Profiling Protein-Protein Interactions in Living Cells

Protein-protein interactions (PPIs) play critical roles in almost all cellular signal transduction events. Characterization of PPIs without interfering with the functions of intact cells is very important for basic biology study and drug developments. However, the ability to profile PPIs especially those weak/transient interactions in their native states remains quite challenging. To this end, many endeavors are being made in developing new methods with high efficiency and strong operability. By coupling with advanced fluorescent microscopy and mass spectroscopy techniques, these strategies not only allow us to visualize the subcellular locations and monitor the functions of protein of interest (POI) in real time, but also enable the profiling and identification of potential unknown interacting partners in high-throughput manner, which greatly facilitates the elucidation of molecular mechanisms underlying numerous pathophysiological processes. In this review, we will summarize the typical methods for PPIs identification in living cells and their principles, advantages and limitations will also be discussed in detail.

Automated summary

Protein-protein interactions (PPIs) are essential for cellular signal transduction. Studying PPIs without disrupting the functions of intact cells is crucial for basic biology research and drug development. Developing new methods with high efficiency and operability, such as advanced fluorescent microscopy and mass spectroscopy techniques, enables the visualization, monitoring, profiling, and identification of PPIs in a high-throughput manner, greatly aiding the understanding of molecular mechanisms underlying various pathophysiological processes.