PXD044504-1

PXD044504 is an original dataset announced via ProteomeXchange.

Title	Structural analysis of PLD3 reveals insights into the mechanism of lysosomal 5' exonuclease-mediated nucleic acid degradation
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:49:57.202.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Tholey
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	2-pyrrolidone-5-carboxylic acid (Gln); monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue; N6,N6-dimethyl-L-lysine
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-11 02:14:47	ID requested
⏵ 1	2024-10-07 13:49:57	announced
2	2024-10-22 06:15:47	announced	2024-10-22: Updated project metadata.

10.1093/NAR/GKAD1114;

submitter keyword: lysosome, phospholipase D, structural biology, DNA/RNA degradation, 5' exonuclease,PLD3

Andreas Tholey
contact affiliation	AG Proteomics & Bioanalytics Institut für Experimentelle Medizin Christian-Albrechts-Universität zu Kiel 24105 Kiel, Germany
contact email	a.tholey@iem.uni-kiel.de
lab head
Andreas Tholey
contact affiliation	Systematic Proteome Research & Bioanalytics, University of Kiel
contact email	a.tholey@iem.uni-kiel.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044504
     1. Label: PRIDE project
     2. Name: Structural analysis of PLD3 reveals insights into the mechanism of lysosomal 5' exonuclease-mediated nucleic acid degradation