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PXD049012

PXD049012 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePhosphorylation of cytosolic hPGK1 affects protein stability and ligand binding: implications for its subcellular targeting in cancer
DescriptionHuman phosphoglycerate kinase 1 is a key glycolytic enzyme that regulates the balance between ADP and ATP concentrations inside the cell. Phosphorylation of hPGK1 at S203 and S256 has been associated with enzyme import from the cytosol to the mitochondria and the nucleus, respectively. These changes in subcellular location drive tumorigenesis and are likely associated with site-specific changes in protein stability. In this work, we investigate the effects of site-specific phosphorylation on thermal and kinetic stability and protein structural dynamics by hydrogen-deuterium exchange (HDX). We also investigate the binding of 3-phosphoglycerate and Mg-ADP using these approaches. We show that the phosphomimetic mutation S256D reduces hPGK1 kinetic stability by 50-fold, with no effect of the mutation S203D. Calorimetric studies of ligand binding show a large decrease in affinity for Mg-ADP in the S256D variant whereas Mg-ADP binding to the WT and S203D can be accurately investigated using protein kinetic stability and binding thermodynamic models. HDX studies structurally confirmed the destabilization caused by the mutation S256D (with some long-range effects on stability) and its reduced affinity for Mg-ADP due to the strong destabilization of its binding site (particularly in the apo-state). Our work thus support that alterations in protein stability might facilitate import of hPGK1 to the nucleus in cancer, whereas the structural and energetic basis of its mitochondrial import remain unknown. The general implications of our work for protein import to certain subcellular locations are discussed in a wider context.
HostingRepositoryPRIDE
AnnounceDate2024-09-07
AnnouncementXMLSubmission_2024-09-07_03:32:13.336.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPavla Vankova
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-01-30 08:09:43ID requested
12024-09-07 03:32:13announced
Publication List
10.1111/FEBS.17262;
Keyword List
ProteomeXchange project tag: EPIC-XS, Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project
submitter keyword: protein phosphorylation
protein stability
ligand binding
cancer
phosphoglycerate kinase
Contact List
Petr Man
contact affiliationInstitute of Microbiology - BioCeV, Academy of Sciences of the Czech Republic
contact emailpman@biomed.cas.cz
lab head
Pavla Vankova
contact affiliationInstitute of Biotechnology of the Czech Academy of Sciences, BioCeV, Prumyslova 595, 252 50 Vestec, Czech Republic
contact emailpavla.vankova@ibt.cas.cz
dataset submitter
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Dataset FTP location
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