PXD072965 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Post-translational regulation of human D-3-phosphoglycerate dehydrogenase in Alzheimer’s disease |
| Description | Emerging evidence suggests that sex-specific differences in L-serine (L-Ser) metabolism play a key role in Alzheimer’s disease (AD). While disruptions in amino acid balance are well known, recent findings point to a dimorphic regulation of the serine biosynthetic pathway. To explore this, we examined post-translational modifications (PTMs) of D-3-phosphoglycerate dehydrogenase (PHGDH) —the rate-limiting enzyme for de novo L-Ser synthesis— as a potential mechanism underlying this difference. PHGDH was immunoprecipitated from hippocampal tissue of healthy and AD-affected males and females and analyzed by mass spectrometry. Five phosphorylation sites (S55, T60, T78, S383, S473) were shared across all groups, but a unique deacetylation at K289 appeared exclusively in AD males. Functional assays using recombinant PHGDH variants revealed that changes at solvent-exposed sites (K289, S383, S473) reduced solubility, while phosphomimetic substitutions at S55 and T78 within the catalytic cleft strongly impaired activity. Notably, mimicking acetylation at K289 improved protein stability. Overall, these PTMs act as subtle modulators rather than on/off switches, fine-tuning PHGDH function and potentially contributing to sex-dependent metabolic vulnerability in AD. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-02-23 |
| AnnouncementXML | Submission_2026-02-22_16:23:44.895.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Simona Nonnis |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | phosphorylated residue; acetylated residue; deamidated residue; iodoacetamide derivatized residue |
| Instrument | Q Exactive |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2026-01-12 11:08:56 | ID requested | |
| ⏵ 1 | 2026-02-22 16:23:45 | announced | |
Publication List
| Zerbini E, Riva D, Maffioli E, Tedeschi G, Sacchi S, Pollegioni L, Post-translational regulation of human D-3-phosphoglycerate dehydrogenase in Alzheimer's disease. Protein Sci, 35(3):e70505(2026) [pubmed] |
| 10.1002/pro.70505; |
Keyword List
| submitter keyword: Proteomics |
| nanoLC-MS/MS |
Contact List
| elisa maffioli |
|---|
| contact affiliation | DIVAS, Department of Veterinary Medicine and Animal Sciences |
| contact email | elisa.maffioli@unimi.it |
| lab head | |
| Simona Nonnis |
|---|
| contact affiliation | University of Milan |
| contact email | simona.nonnis@unimi.it |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD072965
- Label: PRIDE project
- Name: Post-translational regulation of human D-3-phosphoglycerate dehydrogenase in Alzheimer’s disease
