The study of protein-protein interactions is crucial for understanding cellular functions and processes in multicellular organisms. However, current methods often lack cellular context, making it difficult to study interactions in tissue-specific environments. This limitation inspired a collaborative research team at The University of Hong Kong to develop a novel approach called Methionine Analog-based Cell-Specific Proteomics and Interactomics (MACSPI).

The team’s approach involves labeling proteins from specific cells with a bifunctional amino acid probe that allows for the isolation and capture of protein-protein interactions through photo-crosslinking. By using a novel unnatural amino acid, photo-ANA, that can be incorporated into proteins by an engineered enzyme, the team was able to selectively label proteins from specific tissues and capture tissue-specific protein complexes.

As a proof-of-concept, the team applied the MACSPI method to profile proteins from muscle cells and neurons in C. elegans, a model organism. They identified many novel tissue-specific proteins and demonstrated the method’s utility in capturing tissue-specific protein-protein interactions. For example, the team identified tissue-specific interactors of the molecular chaperone HSP90, showing that HSP90 binds to distinct sets of proteins to regulate different biological processes in muscles and neurons.

The development of the MACSPI method represents a groundbreaking advancement in the study of protein-protein interactions in multicellular organisms. By allowing for the profiling of proteomes and interactomes with spatial and temporal specificity, this approach can facilitate a wide range of biological and biomedical research. The team envisions that this method will play a critical role in deciphering the molecular mechanisms of various biological processes and diseases, such as neurodegeneration in Parkinson’s disease.

The innovative MACSPI method developed by the research team at The University of Hong Kong represents a significant breakthrough in the field of protein-protein interaction research. By enabling the study of interactions in tissue-specific contexts, this approach opens up new opportunities for understanding cellular functions and disease pathogenesis in multicellular organisms. With its potential applications in a wide range of biological and biomedical research, the MACSPI method is poised to revolutionize the way we investigate protein interactions at the cellular level.


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