Proteomic data from human cell cultures refine mechanisms of chaperone-mediated protein homeostasis

Cell Stress Chaperones. 2013 Sep;18(5):591-605. doi: 10.1007/s12192-013-0413-3. Epub 2013 Feb 21.

Abstract

In the crowded environment of human cells, folding of nascent polypeptides and refolding of stress-unfolded proteins is error prone. Accumulation of cytotoxic misfolded and aggregated species may cause cell death, tissue loss, degenerative conformational diseases, and aging. Nevertheless, young cells effectively express a network of molecular chaperones and folding enzymes, termed here "the chaperome," which can prevent formation of potentially harmful misfolded protein conformers and use the energy of adenosine triphosphate (ATP) to rehabilitate already formed toxic aggregates into native functional proteins. In an attempt to extend knowledge of chaperome mechanisms in cellular proteostasis, we performed a meta-analysis of human chaperome using high-throughput proteomic data from 11 immortalized human cell lines. Chaperome polypeptides were about 10% of total protein mass of human cells, half of which were Hsp90s and Hsp70s. Knowledge of cellular concentrations and ratios among chaperome polypeptides provided a novel basis to understand mechanisms by which the Hsp60, Hsp70, Hsp90, and small heat shock proteins (HSPs), in collaboration with cochaperones and folding enzymes, assist de novo protein folding, import polypeptides into organelles, unfold stress-destabilized toxic conformers, and control the conformal activity of native proteins in the crowded environment of the cell. Proteomic data also provided means to distinguish between stable components of chaperone core machineries and dynamic regulatory cochaperones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Cell Line
  • Chaperonin 60 / analysis
  • Cytosol / metabolism
  • Endoplasmic Reticulum / metabolism
  • HSP70 Heat-Shock Proteins / analysis
  • HSP90 Heat-Shock Proteins / analysis
  • HeLa Cells
  • Humans
  • Isotope Labeling
  • Mass Spectrometry
  • Mitochondria / metabolism
  • Molecular Chaperones / metabolism*
  • Proteomics*

Substances

  • Amino Acids
  • Chaperonin 60
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones