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PXD061021

PXD061021 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMolecular Structure and Enzymatic Mechanism of the Human Collagen Hydroxylysine Galactosyltransferase GLT25D1/COLGALT1
DescriptionDuring collagen biosynthesis, lysine residues undergo extensive post-translational modifications through the alternate action of two distinct metal ion-dependent enzyme families (i.e., LH/PLODs and GLT25D/COLGALT), ultimately producing the highly conserved alpha-(1,2)-glucosyl-beta-(1,2)-galactosyl-5-hydroxylysine pattern. Malfunctions in these enzymes are linked to developmental pathologies and extracellular matrix alterations associated to enhanced aggressiveness of solid tumors. Here, we characterized human GLT25D1/COLGALT1, revealing an elongated head-to-head homodimeric assembly. Each monomer encompasses two domains (GT1 and GT2), both unexpectedly capable of binding metal ion cofactors and UDP-alpha-galactose donor substrates, resulting in four candidate catalytic sites per dimer. We identified the catalytic site in GT2, featuring an unusual Glu-Asp-Asp motif critical for Mn2+ binding, ruling out direct catalytic roles for the GT1 domain, but showing that the unexpectedly bound Ca2+ and UDP-alpha-galactose cofactors are critical for folding stability. Dimerization was not essential for GLT25D1/COLGALT1 activity, but rather a hallmark for multi-enzyme assembly interactions and/or collagen substrate recognition.
HostingRepositoryPRIDE
AnnounceDate2025-03-05
AnnouncementXMLSubmission_2025-03-05_02:17:40.921.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD061021
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterAlice Vetrano
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-02-20 14:09:01ID requested
12025-03-05 02:17:41announced
Publication List
10.6019/PXD061021;
Keyword List
submitter keyword: Glycosyltransferase,Collagen Biosynthesis
Extracellular Matrix
Post-translational modifications
Contact List
Claudio Iacobucci
contact affiliationUniversity of L'Aquila
contact emailclaudio.iacobucci@univaq.it
lab head
Alice Vetrano
contact affiliationUniversity of L'Aquila
contact emailalice.vetrano@univaq.it
dataset submitter
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Dataset FTP location
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