Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation

Significance How do bacteria adapt to the diverse thermal niches on earth? Evidence accumulates in the protein sequence and structural determinants of thermosensitivity and mechanisms by which molecular chaperones aid protein folding. However, a comprehensive understanding of how thermoadaptation is achieved at the systems level is still missing. Here we reconstruct an integrated genome-scale protein-folding network for Escherichia coli , termed FoldME, that couples both contributing factors to the metabolic state of a cell. FoldME simulations reproduce the asymmetrical bacterial temperature response and delineate the multiscale strategies cells use to resist unfolding stresses induced by high temperature and destabilizing mutations in a single gene. The results highlight how global proteome allocation regulates thermoadaptation through balance between chaperones for folding and translational machinery for biosynthesis.