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Journal Article

The protein targeting factor Get3 functions as ATP-independent chaperone under oxidative stress conditions.

Fulltext (public)

2076348.pdf
(Publisher version), 3MB

Supplementary Material (public)

2076348_Suppl_1.pdf
(Supplementary material), 8MB

2076348_Suppl_2.xls
(Supplementary material), 2MB

2076348_Suppl_3.pdf
(Supplementary material), 11MB

Citation

Voth, W., Schick, M., Gates, S., Li, S., Vilardi, F., Gostimskaya, I., et al. (2014). The protein targeting factor Get3 functions as ATP-independent chaperone under oxidative stress conditions. Molecular Cell, 56(1), 116-127. doi:10.1016/j.molcel.2014.08.017.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0024-46EC-5
Abstract
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.