Details

Autor(en) / Beteiligte

• Voth, Wilhelm
• Schick, Markus
• Gates, Stephanie
• Li, Sheng
• Vilardi, Fabio
• Gostimskaya, Irina
• Southworth, Daniel R.
• Schwappach, Blanche
• Jakob, Ursula

Titel

The Protein Targeting Factor Get3 Functions as ATP-Independent Chaperone under Oxidative Stress Conditions

Ist Teil von

• Molecular cell, 2014-10, Vol.56 (1), p.116-127

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Tail-anchored protein binding factor Get3 functions as redox-regulated chaperone•Chaperone-active Get3 shows major structural changes and loss of ATPase activity•Binding of tail-anchored proteins and chaperone clients appears mutually exclusive•Get3’s chaperone function specifically contributes to oxidative stress survival Oxidative stress threatens proteins, the workhorses in cells. It is poorly understood how eukaryotic cells deal with this challenge. Voth et al. demonstrate that Get3, a protein involved in tail-anchored membrane protein biogenesis, undergoes major structural changes and serves as effective ATP-independent chaperone when oxidized, increasing chaperoning capacity of cells.