Features of the Chaperone Cellular Network Revealed through Systematic Interaction Mapping

Cell Rep. 2017 Sep 12;20(11):2735-2748. doi: 10.1016/j.celrep.2017.08.074.

Abstract

A comprehensive view of molecular chaperone function in the cell was obtained through a systematic global integrative network approach based on physical (protein-protein) and genetic (gene-gene or epistatic) interaction mapping. This allowed us to decipher interactions involving all core chaperones (67) and cochaperones (15) of Saccharomyces cerevisiae. Our analysis revealed the presence of a large chaperone functional supercomplex, which we named the naturally joined (NAJ) chaperone complex, encompassing Hsp40, Hsp70, Hsp90, AAA+, CCT, and small Hsps. We further found that many chaperones interact with proteins that form foci or condensates under stress conditions. Using an in vitro reconstitution approach, we demonstrate condensate formation for the highly conserved AAA+ ATPases Rvb1 and Rvb2, which are part of the R2TP complex that interacts with Hsp90. This expanded view of the chaperone network in the cell clearly demonstrates the distinction between chaperones having broad versus narrow substrate specificities in protein homeostasis.

Keywords: Hsp90; NAJ chaperone complex; R2TP; Rvb1; Rvb2; chaperone network; genetic interaction profiles; genetic interactions; perinuclear condensate; physical interactions.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Epistasis, Genetic
  • Gene Regulatory Networks
  • Genes, Essential
  • HSP90 Heat-Shock Proteins / metabolism
  • Hydrogen-Ion Concentration
  • Molecular Chaperones / metabolism*
  • Protein Binding
  • Protein Interaction Mapping / methods*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Stress, Physiological

Substances

  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones
  • Saccharomyces cerevisiae Proteins
  • Adenosine Triphosphate