Features of the Chaperone Cellular Network Revealed through Systematic Interaction Mapping

Publication date: 12 September 2017
Source:Cell Reports, Volume 20, Issue 11
Author(s): 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
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.

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Teaser

Rizzolo et al. use a systematic integrative approach combining physical and genetic interaction data to construct a comprehensive chaperone network. This analysis revealed the presence of a large functional chaperone supercomplex, the NAJ complex. Furthermore, many chaperone interactors were found to form condensates.


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