O-GlcNAc modification of HSP27 alters its protein interactions and promotes refolding of proteins through the BAG3/HSP70 co-chaperone
Name
Protein Science - 2024 - Javed - O‐GlcNAc modification of HSP27 alters its protein interactions and promotes refolding of.pdf
Description
Published version
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2.88 MB
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Author(s)
Javed, Afraah
Johnson, Oleta T
Balana, Aaron T
Volk, Regan F
Langen, Andreas
Ahn, Benjamin S
Zaro, Balyn W
Gestwicki, Jason E
Pratt, Matthew R
Date Issued
September 18, 2024
Journal
Protein Science
Publisher
Wiley
Citation
Javed A, Johnson OT, Balana AT, Volk RF, Langen A, Ahn BS, et al. O-GlcNAc modification of HSP27 alters its protein interactions and promotes refolding of proteins through the BAG3/HSP70 co-chaperone. Protein Science. 2024; 33(10):e5173.
Version
Final published version
Abstract
Almost all types of cellular stress induce post‐translational O‐GlcNAc modifications of proteins, and this increase promotes cell survival. We previously demonstrated that O‐GlcNAc on certain small heat shock proteins (sHSPs), including HSP27, directly increases their chaperone activity as one potential protective mechanism. Here, we furthered our use of synthetic proteins to prepare biotinylated sHSPs and show that O‐GlcNAc modification of HSP27 also changes how it interacts within the sHSP system and the broader HSP network. Specifically, we show that O‐GlcNAc modified HSP27 binds more strongly to the co‐chaperone protein BAG3, which then promotes refolding of a model substrate by HSP70. We use proteomics to identify other potential HSP27 interactions that are changed by O‐GlcNAc, including one that we confirm with another sHSP, αB‐crystallin. These findings add additional evidence for O‐GlcNAc as a switch for regulating protein–protein interactions and for modifications of chaperones as one mechanism by which O‐GlcNAc protects against protein aggregation.
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Creative Commons Attribution-NonCommercial
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DOI of Published Version
https://doi.org/10.1002/pro.5173
