Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 295, Issue 2, Pages 552-569Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA119.010125
Keywords
70-kilodalton heat-shock protein (Hsp70); chaperone; methionine; redox regulation; post-translational modification (PTM); reactive oxygen species (ROS); Fes1; methionine oxidation; methionine sulfoxide reductase; nucleotide-exchange factor (NEF)
Categories
Funding
- National Institutes of Health [R01 GM105958, T32 GM008500]
- Cornell Schwartz Research Fund Award
- Cornell Presidential Life Science Fellowship
Ask authors/readers for more resources
Cells employ a vast network of regulatory pathways to manage intracellular levels of reactive oxygen species (ROS). An effectual means used by cells to control these regulatory systems are sulfur-based redox switches, which consist of protein cysteine or methionine residues that become transiently oxidized when intracellular ROS levels increase. Here, we describe a methionine-based oxidation event involving the yeast cytoplasmic Hsp70 co-chaperone Fes1. We show that Fes1 undergoes reversible methionine oxidation during excessively-oxidizing cellular conditions, and we map the site of this oxidation to a cluster of three methionine residues in the Fes1 core domain. Making use of recombinant proteins and a variety of in vitro assays, we establish that oxidation inhibits Fes1 activity and, correspondingly, alters Hsp70 activity. Moreover, we demonstrate in vitro and in cells that Fes1 oxidation is reversible and is regulated by the cytoplasmic methionine sulfoxide reductase Mxr1 (MsrA) and a previously unidentified cytoplasmic pool of the reductase Mxr2 (MsrB). We speculate that inactivation of Fes1 activity during excessively-oxidizing conditions may help maintain protein-folding homeostasis in a suboptimal cellular folding environment. The characterization of Fes1 oxidation during cellular stress provides a new perspective as to how the activities of the cytoplasmic Hsp70 chaperones may be attuned by fluctuations in cellular ROS levels and provides further insight into how cells use methionine-based redox switches to sense and respond to oxidative stress.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available