Recently, a collaborative effort between researchers led by Dr. Yu Liu and Dr. Lihua Zhang at the Dalian Institute of Chemical Physics, Chinese Academy of Sciences, has resulted in the development of a targeted proximity labeling and cross-linking method for aggregated protein assemblies within live cells. This achievement was made possible through the screening and structural optimization of organic small molecule photosensitizers. The method enables the in-situ analysis of the composition and interaction information of these protein assemblies. The findings have been published in the journal "Advanced Science."
Proteins require folding into specific three-dimensional structures to perform their physiological functions accurately. However, under conditions such as genetic mutations or stress, proteins are prone to misfolding, aggregation, and ultimately forming insoluble protein aggregates. This physiological phenomenon contributes to protein conformational diseases such as neurodegenerative disorders, metabolic disorders, and cancer. Revealing the location, morphology, composition, and interaction information of aggregated protein assemblies is crucial for understanding the pathogenesis of these diseases and identifying new diagnostic and therapeutic targets.
In this study, the collaboration between Dr. Liu and Dr. Zhang's teams led to the discovery of organic small molecule scaffolds with strong affinity for aggregated protein assemblies through the screening of organic small molecule photosensitizers. This discovery enabled the identification of the components and interaction networks of intracellular aggregated protein assemblies. Dr. Liu's team, starting from traditional organic photosensitizer scaffold structures, identified molecules with high hydrophobicity that exhibit increased binding affinity for aggregated protein assemblies and applied them to proximity labeling and targeted in-situ cross-linking of these assemblies within cells. Dr. Zhang's team established novel methods for the separation, enrichment, proteomics, and cross-linking mass spectrometry analysis of aggregated protein assemblies under drug-induced stress conditions, revealing their components and interaction networks.
This work provides a new analytical method for studying pathogenic aggregated protein assemblies in neurodegenerative diseases.
Related Paper: https://doi.org/10.1002/advs.202306950
