PXD029410 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Parkinson's disease protein PARK7 prevents metabolite and protein damage caused by a glycolytic metabolite |
Description | Early-onset Parkinson's disease can be caused by mutations in the gene PARK7. Many functions have been proposed for PARK7, but in vivo evidence is largely lacking or conflicting with enzymological data. Here, we provide unequivocal evidence that PARK7 and its orthologues can prevent damage of proteins and metabolites inflicted by the glycolytic intermediate 1,3-bisphosphoglycerate, without changing the abundance of this metabolite. In the absence of PARK7, several glycerate-modified metabolites, as well as numerous glycerate- or phosphoglycerate-modified proteins accumulate in human cell lines, mouse brain and flies. This gives an explanation for the pleiotropic effects of PARK7, indicates that spontaneous metabolic damage contributes to the development of hereditary Parkinson's disease, and opens new roads for future therapeutic approaches. Submitted here are the proteomics analyses, where we identify and quantify glyceroyl- and phosphoglyceroyl-modifications of lysine residues in 5 different experimental models. 1. The human colorectal cancer cell line HCT116 was analyzed in four different conditions: a. Wild type cells transduced with an empty recombinant empty lentivirus b. PARK7 knockout cells transduced with an empty recombinant empty lentivirus c. PARK7 knockout cells transduced with a recombinant lentivirus driving expression of PARK7. 2. Brain samples from wild type and PARK7 knockout mice. 3. Red blood cell lysates from wild type and PARK7 knockout mice 4. Whole body extracts from wild type and DJ1beta knockout Drosophila melanogaster 5. In vitro reactions where 1,3-bisphosphoglycerate was produced either by GAPDH or PGK, in the presence and absence of PARK7. Samples were a. Enzymes in the absence of any cofactors (i.e. no 1,3-BPG production) b. Production via GAPDH (using glyceraldehyde 3-phosphate, phosphate and NAD+ as substrates) in the presence or absence of PARK7 c. Production via PGK (using 3-phosphoglycerate and ATP as substrates) in the presence or absence of PARK7. |
HostingRepository | PRIDE |
AnnounceDate | 2022-01-26 |
AnnouncementXML | Submission_2022-01-26_11:39:56.563.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Isaac Heremans |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Oryctolagus cuniculus; NCBI TaxID: 9986; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932; scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227; |
ModificationList | N6-(3-phosphoglyceryl)-L-lysine; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-10-28 08:53:10 | ID requested | |
1 | 2022-01-26 07:25:32 | announced | |
⏵ 2 | 2022-01-26 11:39:57 | announced | 2022-01-26: Updated publication reference for PubMed record(s): 35046029. |
Publication List
Heremans IP, Caligiore F, Gerin I, Bury M, Lutz M, Graff J, Stroobant V, Vertommen D, Teleman AA, Van Schaftingen E, Bommer GT, Parkinson's disease protein PARK7 prevents metabolite and protein damage caused by a glycolytic metabolite. Proc Natl Acad Sci U S A, 119(4):(2022) [pubmed] |
Keyword List
submitter keyword: glycolysis, PARK7, DJ1, Parkinson's disease, posttranslational modification, glycerate, phosphoglycerate, glyceroyl, phosphoglyceroyl |
Contact List
Guido Thomas Bommer |
contact affiliation | Groupe de recherche Metabolique (GRM), BCHM, Institut de Duve, Université Catholique de Louvain, Belgium |
contact email | guido.bommer@uclouvain.be |
lab head | |
Isaac Heremans |
contact affiliation | Université Catholique de Louvain Institut de Duve |
contact email | isaac.heremans@uclouvain.be |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
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[ - ]
- PRIDE
- PXD029410
- Label: PRIDE project
- Name: Parkinson's disease protein PARK7 prevents metabolite and protein damage caused by a glycolytic metabolite