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

Abstract

Taking the heat together Many of the processes in living cells are mediated by protein complexes that dynamically assemble and dissociate depending on cellular needs. Tan et al. developed a method called thermal proximity coaggregation (TPCA) to monitor the dynamics of native protein complexes inside cells (see the Perspective by Li et al. ). The method is based on the idea that proteins within a complex will coaggregate upon heat denaturation. It uses a previously described cellular shift assay to determine melting curves for thousands of proteins and assigns a TPCA signature on the basis of similarity between the curves. The method was validated by detection of many known protein complexes. It identified cell-specific interactions in six cell lines, highlighting the potential for identifying protein complexes that are modulated by disease. Science , this issue p. 1170 ; see also p. 1105