Features of the Chaperone Cellular Network Revealed through Systematic Interaction Mapping

Kamran Rizzolo, Jennifer Huen, Ashwani Kumar, Sadhna Phanse, James Vlasblom, Yoshito Kakihara, Hussein A. Zeineddine, Zoran Minic, Jamie Snider, Wen Wang, Carles Pons, Thiago V. Seraphim, Edgar Erik Boczek, Simon Alberti, Michael Costanzo, Chad L. Myers, Igor Stagljar, Charles Boone, Mohan Babu, Walid A. Houry

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2735-2748
Number of pages14
JournalCell reports
Volume20
Issue number11
DOIs
StatePublished - Sep 12 2017

Bibliographical note

Publisher Copyright:
© 2017 The Author(s)

Keywords

  • Hsp90
  • NAJ chaperone complex
  • R2TP
  • Rvb1
  • Rvb2
  • chaperone network
  • genetic interaction profiles
  • genetic interactions
  • perinuclear condensate
  • physical interactions

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