A Role of Metastable Regions and Their Connectivity in the Inactivation of a Redox-Regulated Chaperone and Its Inter-Chaperone Crosstalk

Oded Rimon, Ohad Suss, Mor Goldenberg, Rosi Fassler, Ohad Yogev, Hadar Amartely, Guy Propper, Assaf Friedler, Dana Reichmann*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Aims: A recently discovered group of conditionally disordered chaperones share a very unique feature; they need to lose structure to become active as chaperones. This activation mechanism makes these chaperones particularly suited to respond to protein-unfolding stress conditions, such as oxidative unfolding. However, the role of this disorder in stress-related activation, chaperone function, and the crosstalk with other chaperone systems is not yet clear. Here, we focus on one of the members of the conditionally disordered chaperones, a thiol-redox switch of the bacterial proteostasis system, Hsp33. Results: By modifying the Hsp33's sequence, we reveal that the metastable region has evolved to abolish redox-dependent chaperone activity, rather than enhance binding affinity for client proteins. The intrinsically disordered region of Hsp33 serves as an anchor for the reduced, inactive state of Hsp33, and it dramatically affects the crosstalk with the synergetic chaperone system, DnaK/J. Using mass spectrometry, we describe the role that the metastable region plays in determining client specificity during normal and oxidative stress conditions in the cell. Innovation and Conclusion: We uncover a new role of protein plasticity in Hsp33's inactivation, client specificity, crosstalk with the synergistic chaperone system DnaK/J, and oxidative stress-specific interactions in bacteria. Our results also suggest that Hsp33 might serve as a member of the house-keeping proteostasis machinery, tasked with maintaining a "healthy" proteome during normal conditions, and that this function does not depend on the metastable linker region.

Original languageAmerican English
Pages (from-to)1252-1267
Number of pages16
JournalAntioxidants and Redox Signaling
Volume27
Issue number15
DOIs
StatePublished - 20 Nov 2017

Bibliographical note

Publisher Copyright:
© Copyright 2017, Mary Ann Liebert, Inc. 2017.

Keywords

  • ATP-independent chaperone
  • Hsp33
  • intrinsically disordered proteins
  • protein thiol switches
  • redox-regulated chaperone

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