title: A Role of Metastable Regions and Their Connectivity in the Inactivation of a Redox-Regulated Chaperone and Its Inter-Chaperone Crosstalk.
abstract: OBJECTIVE
  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. Antioxid. Redox Signal. 27, 1252-1267.
authors.affiliation: 1 Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Safra Campus Givat Ram, The Hebrew University of Jerusalem , Jerusalem, Israel .
authors.forename: Oded
authors.initials: O
authors.lastname: Rimon
authors.affiliation: 1 Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Safra Campus Givat Ram, The Hebrew University of Jerusalem , Jerusalem, Israel .
authors.forename: Ohad
authors.initials: O
authors.lastname: Suss
authors.affiliation: 1 Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Safra Campus Givat Ram, The Hebrew University of Jerusalem , Jerusalem, Israel .
authors.forename: Mor
authors.initials: M
authors.lastname: Goldenberg
authors.affiliation: 1 Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Safra Campus Givat Ram, The Hebrew University of Jerusalem , Jerusalem, Israel .
authors.forename: Rosi
authors.initials: R
authors.lastname: Fassler
authors.affiliation: 1 Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Safra Campus Givat Ram, The Hebrew University of Jerusalem , Jerusalem, Israel .
authors.forename: Ohad
authors.initials: O
authors.lastname: Yogev
authors.affiliation: 2 Institute of Chemistry, The Hebrew University of Jerusalem , Safra Campus Givat Ram, Jerusalem, Israel .
authors.forename: Hadar
authors.initials: H
authors.lastname: Amartely
authors.affiliation: 1 Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Safra Campus Givat Ram, The Hebrew University of Jerusalem , Jerusalem, Israel .
authors.forename: Guy
authors.initials: G
authors.lastname: Propper
authors.affiliation: 2 Institute of Chemistry, The Hebrew University of Jerusalem , Safra Campus Givat Ram, Jerusalem, Israel .
authors.forename: Assaf
authors.initials: A
authors.lastname: Friedler
authors.affiliation: 1 Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Safra Campus Givat Ram, The Hebrew University of Jerusalem , Jerusalem, Israel .
authors.forename: Dana
authors.initials: D
authors.lastname: Reichmann
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D018384:Oxidative Stress; D011487:Protein Conformation; D055550:Protein Stability
chemical_list: D001426:Bacterial Proteins; D006360:Heat-Shock Proteins
keywords: ATP-independent chaperone; Hsp33; intrinsically disordered proteins; protein thiol switches; redox-regulated chaperone