O-GlcNAc modification of small heat shock proteins enhances their anti-amyloid chaperone activity.
O-GlcNAc modification of small heat shock proteins enhances their anti-amyloid chaperone activity.
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DOI：
10.1038/s41557-021-00648-8
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发表时间：
2021-05
期刊：
影响因子：
21.8
通讯作者：
Pratt MR
中科院分区：
文献类型：
--
作者：
Balana AT;Levine PM;Craven TW;Mukherjee S;Pedowitz NJ;Moon SP;Takahashi TT;Becker CFW;Baker D;Pratt MR
A major role for the intracellular posttranslational modification O-GlcNAc appears to be the inhibition of protein aggregation. Most of the previous studies in this area have focused on O-GlcNAc modification of the amyloid-forming proteins themselves. Here, we use synthetic protein chemistry to discover that O-GlcNAc also activates the anti-amyloid activity of certain small heat shock proteins (sHSPs), a potentially more important modification event that can act broadly and substoichiometrically. More specifically, we find that O-GlcNAc increases the ability of sHSPs to block the amyloid formation of both α-synuclein and Aβ(1-42). Mechanistically, we show that O-GlcNAc near the sHSP IXI-domain prevents its ability to intramolecularly compete with substrate binding. Finally, we find that although O-GlcNAc levels are globally reduced in Alzheimer’s disease brains, the modification of relevant sHSPs is either maintained or increased, suggesting a mechanism to maintain these potentially protective O-GlcNAc modifications. Our results have important implications for neurodegenerative diseases associated with amyloid formation and potentially other areas of sHSP biology.
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DOI：
10.1098/rstb.2011.0405
发表时间：
2013-05-05
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Hilton GR;Hochberg GK;Laganowsky A;McGinnigle SI;Baldwin AJ;Benesch JL
通讯作者：
Benesch JL
HSP27易位至肝癌细胞核可能与磷酸化和O-GlcNAc糖基化有关
影响因子：
4.2
作者：
Guo, Kun;Gan, Lin;Liu, Kun Yin
通讯作者：
Liu, Kun Yin
影响因子：
4
作者：
Lewis YE;Galesic A;Levine PM;De Leon CA;Lamiri N;Brennan CK;Pratt MR
通讯作者：
Pratt MR
DOI：
10.1073/pnas.1808845116
发表时间：
2019-01-29
影响因子：
11.1
作者：
Levine, Paul M.;Galesic, Ana;Pratt, Matthew R.
通讯作者：
Pratt, Matthew R.
影响因子：
3.3
作者：
Deracinois, Barbara;Camoin, Luc;Cieniewski-Bernard, Caroline
通讯作者：
Cieniewski-Bernard, Caroline