Differential proteostatic regulation of insoluble and abundant proteins

Bioinformatics. 2019 Oct 15;35(20):4098-4107. doi: 10.1093/bioinformatics/btz214.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chaperonin 60
  • Escherichia coli
  • Escherichia coli Proteins / metabolism*
  • HSP70 Heat-Shock Proteins
  • Molecular Chaperones


  • Chaperonin 60
  • Escherichia coli Proteins
  • HSP70 Heat-Shock Proteins
  • Molecular Chaperones