PXD058840 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Reversible histone deacetylase activity catalyzes lysine acylation |
Description | The dynamic modification of proteins by many metabolites suggests an intimate link between energy metabolism and post-translational modifications (PTM). For instance, starvation and low-carbohydrate diets lead to the accumulation of the ketone body, β-hydroxybutyrate (BHB), whose blood concentrations increase more than 10-fold into the millimolar range, concomitant with the accumulation of lysine β-hydroxybutyrylation (Kbhb) of proteins. As with other lysine acylations, Kbhb marks can be removed by histone deacetylases (HDACs). Here, we report that class I HDACs unexpectedly catalyze a reverse reaction that generates the Kbhb modification on target proteins. Through mutational analysis, we show a shared reliance on key active site amino acids for classical deacetylation and non-canonical HDAC-catalyzed β-hydroxybutyrylation. Based on these data, we propose that HDACs catalyze a condensation reaction between the free amine group on lysine and BHB, thereby generating the amide bond required for covalent attachment of BHB. Also consistent with reversible HDAC activity, Kbhb formation is driven by mass action and substrate availability. This reversible HDAC activity is not limited to BHB but also extends to multiple short-chain fatty acids and represents a novel mechanism of PTM deposition relevant to metabolically-sensitive proteome modifications. |
HostingRepository | PRIDE |
AnnounceDate | 2025-04-16 |
AnnouncementXML | Submission_2025-04-16_13:53:04.462.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | George M Burslem |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-12-12 23:42:43 | ID requested | |
⏵ 1 | 2025-04-16 13:53:05 | announced | |
Publication List
10.1038/s41589-025-01869-5; |
Tsusaka T, Najar MA, Schwarz B, Bohrnsen E, Oses-Prieto JA, Neudorf H, Lee C, Little JP, Burlingame AL, Bosio CM, Burslem GM, Goldberg EL, Reversible histone deacetylase activity catalyzes lysine acylation. Nat Chem Biol, ():(2025) [pubmed] |
Keyword List
submitter keyword: lysine β-hydroxybutyrylation,post-translational modification |
Contact List
George Burslem |
contact affiliation | University of Pennsylvania |
contact email | George.Burslem@pennmedicine.upenn.edu |
lab head | |
George M Burslem |
contact affiliation | University of Pennsylvania |
contact email | George.Burslem@pennmedicine.upenn.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD058840
- Label: PRIDE project
- Name: Reversible histone deacetylase activity catalyzes lysine acylation