The protein targeting factor Get3 functions as ATP-independent chaperone under oxidative stress conditions
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The protein targeting factor Get3 functions as ATP-independent chaperone under oxidative stress conditions. / Voth, Wilhelm; Schick, Markus; Gates, Stephanie; Li, Sheng; Vilardi, Fabio; Gostimskaya, Irina; Southworth, Daniel R; Schwappach, Blanche; Jakob, Ursula.
in: MOL CELL, Jahrgang 56, Nr. 1, 02.10.2014, S. 116-27.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - The protein targeting factor Get3 functions as ATP-independent chaperone under oxidative stress conditions
AU - Voth, Wilhelm
AU - Schick, Markus
AU - Gates, Stephanie
AU - Li, Sheng
AU - Vilardi, Fabio
AU - Gostimskaya, Irina
AU - Southworth, Daniel R
AU - Schwappach, Blanche
AU - Jakob, Ursula
N1 - Copyright © 2014 Elsevier Inc. All rights reserved.
PY - 2014/10/2
Y1 - 2014/10/2
N2 - Exposure of cells to reactive oxygen species (ROS) causes a rapid and significant drop in intracellular ATP levels. This energy depletion negatively affects ATP-dependent chaperone systems, making ROS-mediated protein unfolding and aggregation a potentially very challenging problem. Here we show that Get3, a protein involved in ATP-dependent targeting of tail-anchored (TA) proteins under nonstress conditions, turns into an effective ATP-independent chaperone when oxidized. Activation of Get3's chaperone function, which is a fully reversible process, involves disulfide bond formation, metal release, and its conversion into distinct, higher oligomeric structures. Mutational studies demonstrate that the chaperone activity of Get3 is functionally distinct from and likely mutually exclusive with its targeting function, and responsible for the oxidative stress-sensitive phenotype that has long been noted for yeast cells lacking functional Get3. These results provide convincing evidence that Get3 functions as a redox-regulated chaperone, effectively protecting eukaryotic cells against oxidative protein damage.
AB - Exposure of cells to reactive oxygen species (ROS) causes a rapid and significant drop in intracellular ATP levels. This energy depletion negatively affects ATP-dependent chaperone systems, making ROS-mediated protein unfolding and aggregation a potentially very challenging problem. Here we show that Get3, a protein involved in ATP-dependent targeting of tail-anchored (TA) proteins under nonstress conditions, turns into an effective ATP-independent chaperone when oxidized. Activation of Get3's chaperone function, which is a fully reversible process, involves disulfide bond formation, metal release, and its conversion into distinct, higher oligomeric structures. Mutational studies demonstrate that the chaperone activity of Get3 is functionally distinct from and likely mutually exclusive with its targeting function, and responsible for the oxidative stress-sensitive phenotype that has long been noted for yeast cells lacking functional Get3. These results provide convincing evidence that Get3 functions as a redox-regulated chaperone, effectively protecting eukaryotic cells against oxidative protein damage.
KW - Adenosine Triphosphatases/chemistry
KW - Adenosine Triphosphate/metabolism
KW - Guanine Nucleotide Exchange Factors/chemistry
KW - Models, Biological
KW - Molecular Chaperones/metabolism
KW - Oxidation-Reduction
KW - Oxidative Stress
KW - Protein Unfolding
KW - Saccharomyces cerevisiae/metabolism
KW - Saccharomyces cerevisiae Proteins/chemistry
U2 - 10.1016/j.molcel.2014.08.017
DO - 10.1016/j.molcel.2014.08.017
M3 - SCORING: Journal article
C2 - 25242142
VL - 56
SP - 116
EP - 127
JO - MOL CELL
JF - MOL CELL
SN - 1097-2765
IS - 1
ER -