The redox-switch domain of Hsp33 functions as dual stress sensor.
The redox-regulated chaperone Hsp33 is specifically activated upon exposure of cells to peroxide stress at elevated temperatures. Here we show that Hsp33 harbors two interdependent stress-sensing regions located in the C-terminal redox-switch domain of Hsp33: a zinc center sensing peroxide stress conditions and an adjacent linker region responding to unfolding conditions. Neither of these sensors works sufficiently in the absence of the other, making the simultaneous presence of both stress conditions a necessary requirement for Hsp33's full activation. Upon activation, Hsp33's redox-switch domain adopts a natively unfolded conformation, thereby exposing hydrophobic surfaces in its N-terminal substrate-binding domain. The specific activation of Hsp33 by the oxidative unfolding of its redox-switch domain makes this chaperone optimally suited to quickly respond to oxidative stress conditions that lead to protein unfolding.
Ilbert
Marianne
M
Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N-University, Ann Arbor, Michigan 48109-1048, USA.
Horst
Janina
J
Ahrens
Sebastian
S
Winter
Jeannette
J
Graf
Paul C F
PC
Lilie
Hauke
H
Jakob
Ursula
U
D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002942:Circular Dichroism; D005453:Fluorescence; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D013058:Mass Spectrometry; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013696:Temperature
D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D006861:Hydrogen Peroxide