title: Cellular proteomes have broad distributions of protein stability.
abstract: Biological cells are extremely sensitive to temperature. What is the mechanism? We compute the thermal stabilities of the whole proteomes of Escherichia coli, yeast, and Caenorhabditis elegans using an analytical model and an extensive database of stabilities of individual proteins. Our results support the hypothesis that a cell's thermal sensitivities arise from the collective instability of its proteins. This model shows a denaturation catastrophe at temperatures of 49-55°C, roughly the thermal death point of mesophiles. Cells live on the edge of a proteostasis catastrophe. According to the model, it is not that the average protein is problematic; it is the tail of the distribution. About 650 of E. coli's 4300 proteins are less than 4 kcal mol(-1) stable to denaturation. And upshifting by only 4° from 37° to 41°C is estimated to destabilize an average protein by nearly 20%. This model also treats effects of denaturants, osmolytes, and other physical stressors. In addition, it predicts the dependence of cellular growth rates on temperature. This approach may be useful for studying physical forces in biological evolution and the role of climate change on biology.
authors.affiliation: Department of Physics and Astronomy, University of Denver, Denver, Colorado, USA. kghosh@du.edu
authors.forename: Kingshuk
authors.initials: K
authors.lastname: Ghosh
authors.forename: Ken
authors.initials: K
authors.lastname: Dill
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002477:Cells / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D012492:Salts / Q000494:pharmacology; D013696:Temperature
chemical_list: D020543:Proteome; D012492:Salts