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PXD044504-1

PXD044504 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructural analysis of PLD3 reveals insights into the mechanism of lysosomal 5' exonuclease-mediated nucleic acid degradation
DescriptionThe phospholipase D (PLD) family is comprised of enzymes bearing phospholipase activity towards lipids or endo- and exonuclease activity towards nucleic acids. PLD3 is synthesized as a type II transmembrane protein and proteolytically cleaved in lysosomes yielding a soluble active form. The deficiency of PLD3 leads to the slowed degradation of nucleic acids in lysosomes and chronic activation of nucleic acid-specific intracellular toll-like receptors. While the mechanism of PLD phospholipase activity has been extensively characterized, not much is known about how PLDs bind and hydrolyze nucleic acids. Here, we determined the high-resolution crystal structure of the luminal N-glycosylated domain of human PLD3 in its apo- and single-stranded DNA-bound forms. PLD3 has a typical phospholipase fold and forms homodimers with two independent catalytic centers via a newly identified dimerization interface. The structure of PLD3 in complex with an ssDNA-derived thymidine product in the catalytic center provides insights into the substrate binding mode of nucleic acids in the PLD family. Our structural data suggest a mechanism for substrate binding and nuclease activity in the PLD family and provide the structural basis to design immunomodulatory drugs targeting PLD3.
HostingRepositoryPRIDE
AnnounceDate2024-10-07
AnnouncementXMLSubmission_2024-10-07_13:49:57.202.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAndreas Tholey
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList2-pyrrolidone-5-carboxylic acid (Gln); monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue; N6,N6-dimethyl-L-lysine
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-11 02:14:47ID requested
12024-10-07 13:49:57announced
22024-10-22 06:15:47announced2024-10-22: Updated project metadata.
Publication List
10.1093/NAR/GKAD1114;
Keyword List
submitter keyword: lysosome, phospholipase D, structural biology, DNA/RNA degradation, 5' exonuclease,PLD3
Contact List
Andreas Tholey
contact affiliationAG Proteomics & Bioanalytics Institut für Experimentelle Medizin Christian-Albrechts-Universität zu Kiel 24105 Kiel, Germany
contact emaila.tholey@iem.uni-kiel.de
lab head
Andreas Tholey
contact affiliationSystematic Proteome Research & Bioanalytics, University of Kiel
contact emaila.tholey@iem.uni-kiel.de
dataset submitter
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Dataset FTP location
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