Thermal proximity coaggregation for system-wide profiling of protein complex dynamics in cells

Chris Soon Heng TanPär Nordlund


Proteins differentially interact with each other across cellular states and conditions but efficient proteome-wide strategy to monitor them is lacking. We report the application of thermal proximity coaggregation (TPCA) for high throughput intracellular monitoring of protein complex dynamics. Significant TPCA signatures observed among well-validated protein-protein interactions correlate positively with interaction stoichiometry, and are statistically observable in more than 350 annotated human protein complexes. Using TPCA, we identify many complexes without detectable differential protein expression, including chromatin-associated complexes, modulated in S-phase of the cell cycle. Comparing six cell lines, TPCA reveals cell-specific interactions even in fundamental cellular processes. TPCA constitutes an approach for system-wide studies of protein complexes in non-engineered cells and tissues, and might be used to identify protein complexes that are modulated in diseases.


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