The redox-switch domain of Hsp33 functions as dual stress sensor

• Published in: Nature structural & molecular biology Vol. 14; no. 6; pp. 556 - 563
• Main Authors: Jakob, Ursula, Ilbert, Marianne, Horst, Janina, Ahrens, Sebastian, Winter, Jeannette, Graf, Paul C F, Lilie, Hauke
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-06-2007
• Subjects: Active oxygen; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacterial Proteins - physiology; Biosensors; Biotechnology; Cellular proteins; Circular Dichroism; Fluorescence; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Heat-Shock Proteins - physiology; High temperature; Hydrogen Peroxide - metabolism; Mass Spectrometry; Models, Molecular; Molecular biology; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Molecular Chaperones - physiology; Mutation - genetics; Oxidative stress; Oxidative Stress - physiology; Physiological aspects; Protein Conformation; Protein Folding; Protein Structure, Tertiary; Proteins; Sensors; Stress; Structure; Temperature; United States
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb1244

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.