MOTIVATION: In vivo protein folding is governed by molecular chaperones, that escort proteins from their translational birth to their proteolytic degradation. In E.coli the main classes of chaperones that interact with the nascent chain are trigger factor, DnaK/J and GroEL/ES and several authors have performed whole-genome experiments to construct exhaustive client lists for each of these. RESULTS: We constructed a database collecting all publicly available data of experimental chaperone-interaction and -dependency data for the E.coli proteome, and enriched it with an extensive set of protein-specific as well as cell context-dependent proteostatic parameters. We made this publicly accessible via a web interface that allows to search for proteins or chaperone client lists, but also to profile user-specified datasets against all the collected parameters. We hope this will accelerate research in this field by quickly identifying differentiating features in datasets. AVAILABILITY AND IMPLEMENTATION: The Protein Homeostasis Database is freely available without any registration requirement at http://PHDB.switchlab.org/.

MOTIVATION: Despite intense effort, it has been difficult to explain chaperone dependencies of proteins from sequence or structural properties. RESULTS: We constructed a database collecting all publicly available data of experimental chaperone interaction and dependency data for the Escherichia coli proteome, and enriched it with an extensive set of protein-specific as well as cell-context-dependent proteostatic parameters. Employing this new resource, we performed a comprehensive meta-analysis of the key determinants of chaperone interaction. Our study confirms that GroEL client proteins are biased toward insoluble proteins of low abundance, but for client proteins of the Trigger Factor/DnaK axis, we instead find that cellular parameters such as high protein abundance, translational efficiency and mRNA turnover are key determinants. We experimentally confirmed the finding that chaperone dependence is a function of translation rate and not protein-intrinsic parameters by tuning chaperone dependence of Green Fluorescent Protein (GFP) in E.coli by synonymous mutations only. The juxtaposition of both protein-intrinsic and cell-contextual chaperone triage mechanisms explains how the E.coli proteome achieves combining reliable production of abundant and conserved proteins, while also enabling the evolution of diverging metabolic functions. AVAILABILITY AND IMPLEMENTATION: The database will be made available via http://phdb.switchlab.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.